A person ’s memory may decline due to age, a high-stress lifestyle, and other common factors. In this post, we’ll be covering ten different supplements and nootropics that have been reported to help improve memory and will break down what the science says about the potential effects and mechanisms behind each one. Read on to start learning more! Disclaimer: This post is not a recommendation or endorsement for the use of any of the particular compounds or drugs discussed in this post. The FDA has not approved any of these compounds for “cognitive-enhancement” purposes, and the available research on them is still in a very early stage overall. We have written this post for informational purposes only, and our goal is solely to inform people about what science currently says about these substances’ potential uses and mechanisms. Supplements and Compounds That May Improve Memory POSSIBLY EFFECTIVE: Compounds that fall into this category are considered to be “possibly effective”. This means that while it’s not 100% certain that they are effective, a fair number of early studies have been done on them, and their findings tend to lean in the direction of suggesting some potential efficacy. Nonetheless, it should be kept in mind that these supplements still have not been officially FDA-approved for any specific purpose, and much more research will still be needed to fully confirm their potential efficacy and overall safety in healthy human users. 1) Huperzine A Huperzine A has been reported to have several neuroprotective effects [ 1]. In addition to these potential brain-protecting effects, some preliminary research also reports that huperzine A may have some effects on specific cognitive functions, such as learning and memory. For example, one early human study reported that huperzine A appeared to enhance the memory and learning of junior middle school students who were complaining of memory problems . Huperzine A has also been reported to be relatively well-tolerated, and showed promising treatment potential (possibly significant memory improvement) in patients with Alzheimer’s disease and vascular dementia, according to one early study [ 3]. Parkinson’s and Alzheimer’s disease patients experience degeneration in the nucleus basalis, a region of the brain that is extremely rich in acetylcholine cells. According to one study in an animal model, Huperzine A was reported to help restore healthy brain electrical activity (EEG). In animals suffering from lesions in this brain region, Huperzine A was also reported to reduce impairments in cognitive and memory functions caused by brain lesions [ 4]. How Huperzine A May Improve Memory : Possibly increasing acetylcholine (specifically, by inhibiting acetylcholinesterase, the enzyme responsible for breaking down and removing this neurotransmitter from the brain) . Potentially increasing the levels of important growth factors such as NGF, BDNF, and TGF-Beta. These compounds are also believed to help protect the brain, and may even possibly improve memory and learning ability . Although huperzine A’s full mechanisms of action are not completely known, early results from one animal study in mice with reduced blood flow to the brain (chronic cerebral hypoperfusion) suggest that Huperzine A treatment may also alleviate cognitive impairment by [ 1]: reducing myelin damage decreasing inflammation (via TNF-alpha) alleviating white matter lesions reducing overall cell damage / cell death preventing or reducing the negative effects of low oxygen (hypoxia) Limited clinical trials suggest that huperzine A helps improve learning and memory, possibly by increasing the neurotransmitter acetylcholine. POSSIBLY INEFFECTIVE: Compounds that fall into this category are considered to be “possibly ineffective”. This means that while a fair amount of early research has been done on them, the findings from these preliminary studies generally report mixed, inconclusive, or even negative results, which cast some doubt on their true potential. Note that this doesn’t necessarily mean that they are not effective – it only means that the data available on them so far leans towards suggesting that they might not be effective as initially believed. As always, more research will be needed to find out for certain whether or not they are potentially effective and safe. 2) Citicoline (CDP-Choline) Citicoline is an important intermediate in the creation of phosphatidylcholine from choline. In some studies, citicoline has been reported to: Improve memory and learning, including situations of impoverished environments (animal studies) [6, 7] Improve cognitive control (a frontal lobe function) in humans [ 8] Reduce memory impairments associated with brain diseases in humans (including chronic cerebrovascular disease, dementia, cerebral insufficiency, memory problems, dementia, and ischemic stroke) [9, 10, eleven ] Some of the potential mechanisms that have been suggested to be behind the effects of citicoline include: Enhances membrane phosphatide synthesis [ 7] Decrease pre-programmed cell death of neurons (apoptosis)  Increases levels of the anti-oxidant compound glutathione, while decreasing levels of oxidized glutathione [ 11] However, other studies had mixed or negative findings. Specifically, citicoline does not seem to improve cognition in healthy people, which is what is usually meant by “nootropic effects. ” Further clinical trials are needed . Until further clinical trials come out, the effects of citicoline on memory enhancement remain uncertain. Some studies had negative findings, which sheds doubt on this supplement ’s potential nootropic benefits. INSUFFICIENT EVIDENCE: Much of the research on the compounds listed below is still in a very early stage, and in most cases, it is not yet possible to come to any firm conclusions about their relative efficacy and safety in human users. Therefore, the potential effects listed below are still considered to have insufficient evidence, and these findings should be taken with a grain of salt until further research work – including large-scale clinical trials in healthy human users – is performed. 3) Panax Ginseng + Ginkgo Biloba Panax ginseng is a traditional Chinese herb that has been claimed by some to improve long-term memory. But does the science back this up? At least one early human study has reported that the ginkgo/ginseng combination to improve memory in healthy adults [ 12]. Ginkgo Biloba has also been reported to have positive effects on dementia and Alzheimer’s disease, as well as long-term memory in general. Although scientists don ’t know for sure how panax ginseng works yet, some preliminary findings suggest that it may improve memory by : Reducing oxidative stress by promoting the release of Nitric Oxide (NO), which protects the brain [ 13] Increasing serotonin [ 14] Increasing the levels of various important neurotransmitters (such as dopamine, epinephrine, and norepinephrine) involved in learning (rat study)  In addition to these general mechanisms, some of the other potential mechanisms that have been suggested to be behind the effects Ginkgo Biloba include : Increasing acetylcholine, which may theoretically help with learning, attention, and memory [ 15, 16] Increasing antioxidant enzymes, such as superoxide dismutase (SOD) and catalase, in the rat hippocampus [ 17] Protecting the mitochondrial membrane and preventing cytochrome c release, preventing neurons from pre-programmed cell death (a process called apoptosis) [ 17] Protecting against amyloid-beta-induced toxicity, which is believed to be one of the most important factors in the development of Alzheimer’s disease  Although ginseng and ginko appeared to improve memory in small human studies, large-scale data are lacking. 4) Bacopa Monnieri According to a handful of early research studies in both animals and humans, supplements containing compounds derived from the bacopa monnieri plant has been reported to improve: Attention, cognitive processing, and working memory (by inhibiting acetylcholinesterase, or AChE) [ 18] Overall memory and general cognitive function (based on auditory and Stroop tasks) [ 19] Free memory recall [ 20] Delayed word call [ 21] Memory acquisition and retention (in older men only) [ 22] Memory formation and retention [ 23] Some of the potential mechanisms that have been suggested to be behind the effects of Bacopa include: Increasing acetylcholine levels (by inhibiting acetylcholinesterase and/or choline acetyltransferase) and glutamate levels, each of which is a neurotransmitter that is believed to play a key role in learning and memory [ 24, 16] Increasing enzymes and transporters that act to increase serotonin (TPH2, SERT) levels, which may play a role in overall learning and memory [ 24] Protecting the brain from oxidative stress by increasing the levels of antioxidant enzymes (such as superoxide dismutase (SOD), catalase, GPx, and GSR) as well as glutathione (one of the brain’s most potent Natural anti-oxidant compounds) [ 24] Increasing brain blood flow by stimulating nitric oxide (NO) production and inhibiting calcium fluctuations. These mechanisms are believed by some to be vital to memory and overall brain health [ 24]Bacopa is traditionally used to boost cognitive abilities, but clinical trials to support this benefit are sparse. ) ButyrateAccording to some researchers, some early evidence suggests that sodium butyrate may place the brain into a state that could potentially benefit long-term memory . For example, sodium butyrate was reported to increase memory function in patients with age-related brain diseases, according to one early clinical trial . Another study has reported that exercise and sodium butyrate together may be able to help weak, newly-formed memories get transferred into more stable long-term memories . Similarly, another study reports that sodium butyrate may help prevent memory impairments in rats subjected to experimental pneumococcal meningitis . According to one animal study, sodium butyrate has been reported to boost long-term memory by increasing synaptic activity in the hippocampus (a region of the brain that is believed to be critical for forming and storing new memories during learning) . However, follow-up studies on butyrate ’s potential mechanisms in healthy human users will be needed to further confirm this early finding. Some of the other potential mechanisms that have been suggested to be behind the effects of butyrate include: Increases BDNF, NGF, and GDNF . Stimulates the growth and development of nerve tissue . Early clinical trials show that butyrate might enhance long-term memory, but additional research is needed to determine its effectiveness. 6) Creatine Creatine‘s main role is recycling cellular energy (in the form of ATP), primarily in the brain and muscles. Creatine is currently in Phase III clinical trials for the treatment of Huntington’s disease . Creatine, both with- or without exercise (synergistic effect when combined), may protect the brain. For example, one study reports that it may help to delay the progression of some major neurodegenerative diseases, such as Alzheimer’s . In elderly patients, creatine supplementation reportedly improved cognition and memory in all but one test, providing additional suggestive evidence that creatine may potentially aid cognitive function in the elderly . Interestingly, creatine was reported to improve IQ, memory, and working memory in vegetarians [34, 35]. Creatine is stored as phosphocreatine, which acts as a high-energy reserve. Phosphocreatine decreases rapidly during brain activity. Supplementing with creatine (2 grams per day for one month) was reported to increase average brain creatine levels by 9.7%. This finding suggests that creatine may act as an energy source for the brain to use during demanding cognitive tasks, such as learning, as well as potentially provide an energy source for the storage of newly-formed memories into long-term memory [ 31]. Some of the other potential mechanisms that have been suggested to be behind the effects of creatine include [ 31, 36]: Protecting against beta-amyloid toxicity in the hippocampus Protecting neurons by maintaining mitochondrial energy production and protecting the mitochondria (by raising mitochondrial membrane potentials, reducing intra-mitochondrial levels of reactive oxygen species (ROS), and reducing calcium levels inside the mitochondria) Based on findings from small human studies, creatine seems to support cognition in elderly people and in vegetarians. This hasn’t been confirmed in larger trials. 7) Glucose Glucose is the brain’s most important primary source of energy. While glucose has many positive cognitive effects, one review suggests that memory, in particular, may be especially dependent on glucose for energy [ 36]. A handful of other studies in both animals and humans have reported that glucose may potentially: Improve memory and attention in college students [ 36] Improve cognitive functions in subjects with different neurodegenerative diseases [ 36, 37] Enhance learning and memory (in healthy young animals and humans) [ 36] Improve verbal memory associated with certain health conditions (such as Alzheimer’s, Parkinson’s, and Huntington’s diseases) [ 36] Impaired blood sugar regulation has been linked to cognitive impairments, especially visual memory. These potential impairments are reported to be relatively worse in older individuals, suggesting that age may be an important factor . Because the brain’s glucose levels are drained by cognitively-demanding tasks, some of these reported cognitive effects may simply be due to restoring the brain ’s energy supply by “re-supplying” it with glucose . Alternatively, glucose-sensitive neurons in the brain may serve as sensors of glucose levels. Therefore, glucose may stimulate these neurons, which may then respond to these signals by stimulating processes related to learning and memory . Some of the other potential mechanisms that have been suggested to be behind the effects of glucose include: Improving memory consolidation and memory coding when task demand is high (this is probably just a downstream effect of increased cellular energy levels) [ 39] Increasing insulin levels, which is linked to memory enhancement  Increasing acetylcholine, which is a critical neurotransmitter for memory and learning processes  Preventing neuronal cell death (apoptosis) [ 36] Glucose is the brain’s main fuel. Brain cells need glucose to carry out cognitively demaning tasks, but the effectiveness and safety of administering glucose to people with cognitive problems is uncertain. 8) Curcumin Curcumin, also commonly known as the spice turmeric, has been linked to a number of potential beneficial effects on the brain, as well as on certain health conditions, such as Alzheimer ’s disease . Reported Benefits for the Brain / Cognitive Function: In older people, long-term supplementation with curcumin has been reported to significantly improve working memory [ 40] May protect against stress-induced impairment of brain development (in rats) [ 41] May prevent learning and memory deficits (in rats treated with sodium metabisulfite) [ 42] Reported Effects in Alzheimer’s Disease: In addition to some of the early evidence suggesting possible effects of curcumin on cognitive processes, curcumin has also shown some early promise as a potential preventive supplement for Alzheimer’s disease . However, these effects have only been reported by animal studies so far , so these will need to be confirmed by corresponding studies in human patients. Some of these early animal findings include: Curcumin was reported to reduce spatial memory impairments in rats caused by the build-up of amyloid beta (a neurotoxic byproduct that is believed to be the main factor behind the development and progression of Alzheimer’s disease) [ 44]. Curcumin reportedly protected against neuronal cell death (apoptosis) in rats, which may be linked to some reduced impairments in learning and memory . Although the mechanisms behind these potential effects of curcumin have not been conclusively determined yet, some of the potential mechanisms that have been suggested include: Reducing levels of TNF-a and iNOS in the hippocampus (after subarachnoid hemorrhage in rats) . In rats with traumatic brain injuries, curcumin has also been reported to help protect and preserve cognitive functioning by [47, 41, 48, 49]: Early human studies suggest that curcumin might prevent cognitive decline and improve memory, but more research is needed. Animal And Cell Research (LACKING EVIDENCE): For the supplements and compounds listed below, what we currently know about their potential effects is based solely on animal- or cell-based studies, and are lacking evidence from any appropriate human trials so far. Therefore, these are only potential “ launching-points” for future clinical studies in humans, and no solid conclusions can be made about these effects in human users until much more additional research is done. Alpha-GPC is a Natural cholinergic compound found in the brain. Alpha-GPC has also been investigated for its potential in treating Alzheimer’s disease and multiple forms of dementia. However, the evidence so far comes only from animal studies (primarily in rats and mice) – and so studies in humans will be needed to see if these preliminary results also hold up in actual human patients. According to one study in mice, alpha-GPC was reported to improve a wide number of memory functions (including working memory, verbal memory learning, and pathway learning in a maze task) . Similarly, another animal study reported that alpha-GPC may improve learning and memory in rats with experimentally-induced amnesia . Some of the potential mechanisms that have been suggested to be behind the effects of alpha-GPC include: Other Approaches to Protecting Memory and Counteracting Cognitive Decline 10) Lifestyle & Dietary ChangesFinally, you may not actually need to experiment with supplements and nootropic drugs in order to see noticeable improvements in memory! There are many common lifestyle and dietary factors that can affect how efficiently the brain works – and, by extension, which can affect specific cognitive functions, such as memory. The following strategies below have shown some evidence for boosting memory, and could be considered as complementary approaches to promoting overall brain health and potentially improving cognitive functioning : Further Reading
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