15 SECOND SUMMARY: Huperzine A (HupA) is a compound extracted from Chinese club moss. It inhibits an enzyme that degrades the learning neurotransmitter acetylcholine – meaning that HupA may increase memory and cognitive function.
Huperzine A has been trialled as a treatment for Alzheimer’s disease and results suggest an improvement of cognitive function, daily living activity, and global clinical assessment. However, the existing research is of limited quality and all authors conclude that more quality large scale controlled trials are warranted to corroborate these findings.
As for the other health claims of HupA, such as ‘memory booster’ and ‘fights free radicals’ among those without a diagnosed memory loss condition, there is limited, if any,epidemiological evidence supporting these claims.
What Is Huperzine A?
Huperzine A (HupA) is a compound extracted (and manipulated) from the Huperzia serrate plant, also known as Chinese club moss. HupA is an acetylcholinesterase inhibitor – meaning that HupA inhibits an enzyme that naturally destroys the learning neurotransmitter acetylcholine (ACh).
In the brain ACh has several functions, including the process of learning and memory formation, the conduction of pain, and regulation of REM sleep cycles. Degeneration of ACh is linked to the onset of Alzheimer’s disease (AD).
HupA is known as a ‘Nootropic’, which refers to a group of drugs/supplements that have an effect on the brain, many of which have gained the nickname ‘smart drugs’. These so called ‘smart drugs’ are claimed to be able to do wonderful things such as enhance your memory, improve cognition, focus, and alertness.
Claims Made About Huperzine A
We would all love it if we could take a supplement that enhances our memory. This exact desire in people has fuelled an entire marketing world around the wonder drug HupA.
To give you an idea, some of the positive claims made about HupA include:
- Treatment of Alzheimer’s disease
- Enhanced memory and cognitive function
- Induce Lucid Dreaming
- Fight free radicals
- Supports both short term “brain boost” needs as well as long-term healthy cognitive function
- Reducing mild memory loss associated with normal aging
- Effectively supports cognition, concentration, and memory
- Protects the neurotransmitter acetylcholine, a messenger molecule in the central and peripheral nervous system.
- Protects the number, size and function of cholinergic neurons.
Quite a list!
But in these situations, being a skeptic and a scientist, I tend to follow the adage that if something sounds too good to be true it usually is.
Let’s look at each of these claims about Huperzine A and see what the evidence says.
What Does The Science Say About Huperzine A?
My analysis for this article focused on the most recent studies (which usually have already considered the results of studies that have been done before it).
In particular I looked for systematic reviews and meta-analyses (which analyse the results of a large number of studies within strict criteria), which have been done specifically on HupA
It is interesting to note that the majority of published studies about HupA come out of China, where HupA has been used for thousands of years. There is very little literature (published studies) on this topic from Western countries. This highlights the fact that the use of HupA has not yet been accepted in modern medicine, along with many other ‘alternative ‘therapies which use herbal derivatives. This does not mean that the Chinese studies are not credible, but the fact that the rest of the medical world has not yet caught on makes me suspect there is a reason for that.
Does Huperzine A Assist In The Treatment of Alzheimer’s disease (AD)?
There have been a handful of review/expert opinion articles on the potential effect of HupA for the treatment of AD, however most of these were published over 5 years ago [1-5].
In general the consensus is that HupA shows promising results in patients with AD, however the studies supporting HupA are often limited by weak study design and further evaluation is warranted.
A Cochrane Review in 2008 concluded with the headline on their website “There is currently insufficient evidence of the effects of Huperzine A for Alzheimer's disease”. This was based on reviewing six trials (a total of AD 454 patients) where results showed that HupA seems to have some beneficial effects on improvement cognitive function, global clinical status, and functional performance.
However, the methodological quality of most included trials was not high and that only one study was of adequate quality and size. The authors conclude that further large randomized multi-centre trials are warranted [6].
A recent meta-analyses (e.g. analysing all the results from other studies) combined data from 20 randomized clinical trials (a total of 1823 AD patients). Overall results showed that HupA appears to have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment. However, the authors state that “the findings should be interpreted with caution due to the poor methodological quality of the included trials” [7].
A similar meta-analysis in 2014 analyzed data from 8 AD trials (733 participants) and 2 vascular dementia (VD) trials (92 participants). Similarly, the conclusion was that HupA could significantly improve cognitive performance in patients with AD or VD. However the authors state “we need to use it [HupA] with caution in the clinical treatment” [8].
Risks Of Huperzine A For Alzheimer Patients
The Mayo Clinic states “The Alzheimer's Association recommends that you not take huperzine A if you're already taking a prescribed cholinesterase inhibitor, such as donepezil (Aricept), rivastigmine (Exelon) or galantamine (Razadyne). Taking both could increase your risk of serious side effects” [9].
This is important as there may be people out there already taking prescribed AD drugs who may think that taking HupA as well won’t do any harm. There is insufficient studies to explore the interaction effects between HupA and other drugs that affect brain function so one should take care when taking any herbal supplement whilst taking prescription medication.
I thought that one expert opinion article in particular summed up the current situation quite well.
Australian academics from the School of Public Health at La Trobe University, and the Brain Sciences Institute at Swinburne University reported that:
“Conventional drug treatment for dementia only provides modest benefits for patients, so patients and their carers often turn to complementary medicines. Early trials showed promise for some compounds but larger better conducted studies have usually failed to confirm these benefits. However, there have been few large-scale interventions using complementary medicines for cognition.” [10].
Bottom Line: In general, studies have shown that HupA could have beneficial effects on improvement of cognitive function, daily living activity, and global clinical assessment among those diagnosed with AD. However, more large scale randomised controlled trials and meta-analyses are warranted before the efficacy of HupA can be ‘proven’ to improve cognitive function among patients with AD.
Does Huperzine A Enhance Memory And/Or Cognitive Function?
HupA is often marketed as a ‘memory booster’ to populations without diagnosed memory loss conditions such as dementia and AD.
In this section I focus only on human studies that have investigated the memory enhancement capabilities of HupA among ‘healthy’ participants without significant memory loss conditions. There is highly limited research in this field and that comes as no surprise.
"This One Study On The Interweb"
There is one study in particular that seems to be hovering around the internet generating a lot of excitement on dozens of ‘health’ websites, and is cited repeatedly as ‘proof’ of the ‘memory boosting’ or ‘memory enhancing ’ claims about HupA.
The title of this article is “Huperzine-A capsules enhance memory and learning performance in 34 pairs of matched adolescent students”. I am sure all the students studying for exams would get excited about this title.
Sorry to burst the marketing bubble on this one, but this study was preliminary and of poor quality – it should never have been published.
It was conducted in 1999 among 68 Chinese students (e.g. 34 pairs) who complained about ‘bad memory’. This is the first limitation of the study. What does it mean that they "complained" about "bad memory". No tests were done on the students to understand what if any memory impairment they were actually suffering from.
The treatment group were given two HupA capsules twice a day for 4 weeks, versus the placebo group (starch and lactose capsules) who had the same treatment schedule. The main outcome measures were memory quotient (MQ) and the Weschler memory scale (WMS), along with a quiz performance of English, Chinese, and mathematics.
From baseline to the end of the trial (4 weeks), results showed that MQ had improved in both groups during the 4 week period, with a greater improvement in the HupA group. There was also an improvement in English and Chinese quizzes among the HupA group, but no improvement in mathematics [11].
And... that's it. That's the sum total of the evidence suggesting a human without Alzheimers might see an improvement in their memory and cognition thanks to HupA. Scientifically speaking, and as far as drugs and their effects go, this is the equivalent of no evidence.
The authors of the Chinese study themselves conclude that “these results are preliminary and further research is required” [11], and it is interesting to note that there have been no similar studies undertaken since this study was published 17 years ago.
A One Day Study That Found No Behavioral Effect
There is however, another study among ‘healthy adults’ that investigated physiological and neurobehavioral effects of cholinesterase inhibition of HupA, galantamine and donepezil.
This study had 84 healthy adults (37 males; 47 females) assigned to one of four groups (placebo, HupA, galantamine, donepezil). On day one of the study the participants underwent baseline blood sample collection (to assess inhibited acetylcholinesterase (AChE) versus butyrylcholinesterase (BChE)) and various neurobehavioral assessments. Then on day two (starting at 10am), blood samples were collected hourly and neurobehavioral assessments performed half-hourly until 6.30pm.
Results showed that HupA and galantamine significantly inhibited AChE (and likely increased acetylcholine levels), however neither compound improved neurobehavioral performance.
It is important to note that this study was conducted only during one day [12].
Interestingly, a Cochrane Review in 2012 investigating trials on the use of HupA to improve mild cognitive impairment reported that they failed to find any trials suitable for the inclusion criteria (randomised, parallel-group, placebo-controlled trials comparing HupA with placebo in patients with MCI) [13].
Bottom Line: There is limited to no research suggesting that HupA enhances memory among ‘healthy’ people who aren’t diagnosed with a memory loss condition.
For drugs to be able to be patented and marketed and prescribed by doctors requires years of research and clinical trials demonstrating their efficacy. There is no way that a drug would be on the market based on the relatively unimpressive results of one single study.
Does Huperzine A Induce Lucid Dreaming?
The OptiMind website [14] states that HupA has the “…ability to increase acetylcholine levels suggests it can also increase lucid dreaming”. So what exactly is lucid dreaming and what is so great about it? According to the website World-of-lucid-dreaming [15], lucid dreaming is “…the ability to consciously observe and/or control your dreams. It transforms your inner dream world into a living alternate reality - where everything you see, hear, feel, taste and even smell is as authentic as real life.”
Surprise, surprise! I noticed on the World-of-lucid-dreaming website that they promote HupA as a supplement that does the following:
- Enhance your dream recall
- Increase the intensity of your dreams
- Add a greater sense of meaning to your dreams
- Help you become more self-aware while dreaming
- Sustain highly vivid and lucid dreams
I tried to find some scientific literature to back these claims and I found nothing! There are simply no published studies on the topic of Huperzine A and lucid dreaming.
Furthermore, there are no published studies investigating ANY “nootropic” drug and it's effects on lucid dreaming.
Bottom Line: There is not a single study, trial, article, or review that even investigates the effects of Huperzine A on dreaming. Any claim that HupA has an effect on dreaming is baseless and irresponsible.
Does Huperzine A Fight Free Radicals?
The OptiMind website [14] also claims that HupA boosts nerve growth factor and “It possesses antioxidant and neuroprotective qualities that are shown to improve cognition”.
I searched all published research for [“huperzine A” “oxidative stress”] (and other similar search terms) and I got 23 articles, most were animal studies (mostly conducted on rats).
Although animal studies are extremely important and provide us with information that can then lead to further epidemiological studies, results from animal studies cannot be translated directly to humans.
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