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19 Potential Ways to Stimulate Synaptic Plasticity

Written by Nattha Wannissorn, PhD | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Nattha Wannissorn, PhD | Last updated:

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“Synaptic plasticity” refers to the brain’s ability to adjust how neurons connect to and “talk” to each other, which in turn affects how the brain processes information. This process is crucial for all forms of learning and memory – but are there ways to “boost” synaptic plasticity in the brain? In this post, we’ll review what the latest science has to say about some dietary compounds and supplements that may potentially affect synaptic plasticity throughout the brain. Read on to learn more!

Synaptic Plasticity: A Quick Review

Synaptic plasticity refers to the brain’s ability to adjust how neurons connect to and “talk” to each other, which in turn affects how the brain processes information.

Synaptic plasticity is critical to our ability to learn and store new knowledge and memories, since the brain has to be able to change its structure in order to encode new information and facts!

Deficits and other changes in the cellular processes underlying synaptic plasticity are also believed to be involved in a wide range of neurological and psychiatric disorders, making it very important for overall brain health and psychological well-being.

P.S: For a more detailed overview of what synaptic plasticity is, how it works, and why it’s important, check out our detailed SelfDecode post all about synaptic plasticity here.

Dietary Compounds And Supplements That May Increase Synaptic Plasticity:

According to some preliminary research, there may be a number of foods and dietary compounds that may support or stimulate synaptic plasticity throughout the brain [1, 2].

However, whether consuming the foods and supplements below can actually result in noticeable changes in cognitive function is still an open question. While there is some early research with promising results so far, a lot more research will be needed to fully confirm these effects in healthy human users, and so far there is “insufficient evidence” to officially recommend these strategies for enhancing cognitive functions or treating diseases. Therefore, these early findings should be taken with a grain of salt until more extensive research is done to figure out their full effects.

With that in mind, let’s see what some of the latest science has to say about some nutritional compounds and dietary supplements that may potentially help boost synaptic plasticity!

INSUFFICIENT EVIDENCE:

1) Polyphenols May Stimulate Synaptic Plasticity

Fruits, vegetables, cereals, and beverages contain natural polyphenols. Grapes, apples, pears, cherries, and berries may contain up to 200-300 mg of polyphenols in each 100-gram serving [3].

Phenolic acids, flavonoids, phenolic amides, resveratrol, lignans, curcumin, rosmarinic acid/caffeic acid, ellagic/gallic acid, and tannins are all specific types of polyphenols [4].

According to some early research, polyphenols possess unique molecular properties that have been reported to reduce oxidative stress, and may even stimulate the activation of molecules that aid in synaptic plasticity [5].

2) Red Wine and Resveratrol May Enhance Learning Ability

Resveratrol is a polyphenol abundant in grapes, red wine, berry fruits, and some nuts [4].

According to some preliminary animal studies, resveratrol has been reported to increase AMPAR protein levels, AMPAR synaptic accumulation, and the strength of excitatory synaptic transmission in the neurons of rats [6].

AMPARs are glutamate-associated receptors that are believed to be particularly important for fast excitatory transmission, and synaptic plasticity in general [6].

In one animal study, resveratrol was reported to significantly enhance the learning ability of diabetic rats. The authors of this study propose that this may be because resveratrol has antioxidant and anti-inflammatory activities, as well as the ability to facilitate hippocampal structural synaptic plasticity [7].

In another study, six weeks of resveratrol supplementation resulted in normalization of the expression of genes implicated in hippocampal neurogenesis and synaptic plasticity in diabetic mice [8].

A few more recent studies have reported that resveratrol may activate the SIRT1 gene, an aging-related gene that is believed to have important anti-inflammatory effects [9, 10].

Additionally, mice born without the brain-specific SIRT1 gene have been reported to show decreased overall synaptic plasticity [11].

3) Green Tea May Improve Memory

The active compounds in green tea are predominantly polyphenols and caffeine. According to one animal study in mice with impaired long-term memory due to abnormal levels of the DYRK1A gene (believed to be involved in learning), green tea polyphenol treatment partially reduced the resulting cognitive deficits [12].

According to a recent review, green tea polyphenols (such as EGCG) may help increase cognitive function and mood, while also protecting against various cognitive and psychiatric disorders [5].

In one 12-participant study (DB-RCT), green tea extract was reported to increase working memory [13].

Additionally, green tea extract was reported to increase both working and spatial memory in an animal study in mice [14].

Flavonoids, a group of major constituents of green tea, have also been reported to inhibit cell death triggered by neurotoxic compounds and an increase in synaptic plasticity, according to another review [15].

4) Berries May Have Anti-Aging Properties

Some recent studies have reported that berries may potentially help improve cognitive functions. Natural compounds found in many types of berries have been reported to reduce inflammation as well as potentially increase cell survival, neurotransmission, and overall neuroplasticity [16].

According to some cell- and animal-based studies, aging animals given a blueberry-enriched diet were reported to show an increase in both long-term potentiation and synaptic strength, up to the levels commonly observed in younger animals [17].

Resveratrol, a phenolic compound abundant in berries, has been reported to protect neurons against amyloid beta-induced toxicity (involved in Alzheimer’s), and may even reduce memory degeneration (in rats) [18].

5) Soy May Improve Spatial-Memory Acquisition

Soy contains plant-derived, non-steroidal compounds with estrogen-like effects (phytoestrogens) [19].

A few preliminary studies have suggested that estrogens may help stimulate learning and memory – at least in women [20, 21].

In another early study, female rats without ovaries (an experimental animal model of menopause) were supplemented with soy germ phytoestrogens, and were reported to perform significantly better in spatial memory acquisition and retention when compared to rats fed on a control diet [22].

However, more research will still be needed to fully confirm these effects in humans, as well as to find out if they might also apply to males as well as females.

6) Cocoa May Improve Synaptic Plasticity

Cocoa powder and chocolate contain a large percentage of flavonoids, which have been reported to [23]:

  • Inhibit neuronal cell death induced by neurotoxins (such as oxygen radicals)
  • Promote neuronal survival
  • Improve synaptic plasticity

Flavonoids in cocoa have also been reported to increase adult hippocampal neurogenesis in chronically-stressed rats [24].

The flavonol quercetin – a major component of cocoa extracts – was reported to improve learning and memory impairments in rats that suffered from a lack oxygen to the brain (hypoxia) [25].

7) Acetyl-L-Carnitine (ALCAR) May Stimulate Synaptic Plasticity

According to one animal study in aging rats, chronic administration of carnitine was reported to increase choline-associated synaptic transmission. According to the study’s authors, this effect may have also led to enhanced learning capacity [26].

In one clinical study (DB-RCT), carnitine was reported to improve a variety of cognitive and other symptoms of Alzheimer’s disease in 1,204 patients at an early stage of disease [27].

Acetyl-L-carnitine has also been reported to increase synaptic strength, as well as stimulate activity-dependent plasticity in sensory networks by increasing the strength of neuronal signals after the synapses (afterhyperpolarization amplitude) [28].

8) Fish Oil (DHA and EPA) May Enhance Learning and Memory

DHA and EPA (omega-3 fatty acids) in fish oil have been reported to potentially enhance synaptic plasticity by [29]:

  • Increasing long-term potentiation
  • Enhancing the creation of new neurons in the hippocampus
  • Increasing production of proteins in the synapses
  • Facilitating the formation of protein complexes that are involved in the transport and release of neurotransmitters into the synapses (also called SNARE complexes) [30]
  • Increasing the density of dendritic spines (the postsynaptic neuron’s appendages that extend to the postsynaptic axons) in the hippocampus [31]

These preliminary findings may suggest that DHA supplementation could help with neurodegenerative diseases and improves brain function – although more research will still be needed in order to fully confirm this [30].

9) Magnesium (Mg) May Prevent Memory Decline in Alzheimer’s disease

Increasing extracellular magnesium within the physiological range has been reported to enhance synaptic plasticity in neurons of the hippocampus [32].

According to one animal study, rats treated with MgT (magnesium-L-threonate) reportedly showed an increase in NMDA neurotransmission, presynaptic connections, and synaptic plasticity in the hippocampus, along with overall memory enhancements [33].

In another study in a mouse model of Alzheimer’s disease, magnesium treatment was reported to reduce the buildup of amyloid-β plaques, and may have prevented the loss (degeneration) of synapses and decline in memory function [34].

10) Zinc (Zn) May Increase Synaptic Plasticity

Zinc is believed to help activate the enzyme extracellular-regulated kinase (ERK) in neurons [35]. This stimulation is believed to help increase overall synaptic plasticity [36].

Zinc is an important mineral for neurotransmitter release from glutamate neurons, suggesting that zinc may be also involved in synaptic plasticity in an even more general way [37].

11) Curcumin May Improve Spacial Memory

According to one preliminary animal study, curcumin (also known as the spice turmeric) was reported to significantly improve spatial memory impairment induced by the HIV-1 virus in rats [38].

Interestingly, some evidence has suggested that curcumin may even help stimulate the creation and development of adult hippocampal neurons, which may enhance overall neuronal plasticity in a general manner [39].

Curcumin has also been associated with increases in DHA levels throughout the brain, which may suggest another potential role for curcumin in enhancing overall learning and memory [40].

12) Berberine May Improve Memory Impairment in Diabetes

According to one early animal study, treatment with berberine was reported to alleviate memory impairments and improve overall synaptic plasticity in rats with streptozotocin-induced diabetes [41].

Some researchers have proposed that berberine may increase synaptic plasticity by reversing synaptic impairment induced by d-galactose [42].

In another study in rats, berberine was reported to help counteract oxidative stress and, consequently, may have led to further improvements in memory impairments [43].

13) Rehmannia May Stimulate the Formation of New Neurons

Rehmannia is an active ingredient in the Rehmannia glutinosa plant. This compound has been reported to improve synaptic plasticity, possibly by inhibiting voltage-dependent calcium channels and increasing the function of NMDA receptors [44].

Catalpol, another major component of the Rehmannia plant, has been reported to increase neuronal plasticity, stimulate the creation of new neurons, and even enhance overall synaptic plasticity [45].

14) Bitter Melon May Reduce Oxidative Stress

According to one early study in mice, bitter melon (Momordica Charantia) was reported to increase levels of the (longevity-associated) SIRT1 gene. The authors of this study propose that this may help reduce oxidative stress throughout the brain, which in turn could potentially help enhance or stimulate overall synaptic plasticity [46].

Additionally, another mouse study reported that bitter melon may also potentially help reduce neuronal inflammation due to obesity [46].

15) Saffron May Be Neuroprotective

According to some preliminary research, saffron may have a number of significant beneficial effects, including neuroprotective effects (protecting the brain and its cells from stress or damage) [47].

Streptozotocin is a neurotoxin that has been reported to reduce the total number of neurons in the hippocampus. According to some researchers, crocin – the pigment that gives saffron its yellow color – may help mitigate memory impairments caused by streptozotocin. Based on this, some have suggested that crocin may be the active component that is responsible for some of saffron’s reported ability to improve learning and memory [48].

16) Uridine May Enhance Cognitive Functions

The rates at which brain neurons form new dendritic spines and synapses depend heavily on the brain’s levels of three major compounds: uridine, DHA, and choline. Therefore, low levels of uridine could theoretically lead to reduced synaptic plasticity [49].

Uridine, administered together with DHA and choline, has been reported to enhance cognitive functions and increase neurotransmitter release in experimental animals, and may have significantly improved memory in 220 patients with Alzheimer’s disease [49].

However, more research will be needed to determine if this effect was specifically due to uridine, or whether some of the other compounds may have been more directly responsible for these findings.

However, results from a handful of cell-based studies suggest that uridine may promote axon growth and bulk transport mechanisms [50, 51, 52], which are important processes in synaptic plasticity. Therefore, this could be one mechanism that might help account for some of the uridine-related findings mentioned above.

17) Fasting May Induce Autonomic Synaptic Plasticity

Fasting causes a form of autonomic synaptic plasticity that prevents low blood sugar [53].

Furthermore, fasting stimulates AMPK activity required by hypothalamic AgRP neurons [54, 55].

According to one early animal study, AMPK activity in the hypothalamus was reported to be higher in mice who fasted compared to normally-fed mice [56].

Moreover, a fasting-induced increase in ketone bodies has been associated with potentially beneficial changes in neuronal excitability and neurotransmitter release throughout the brain [57, 58].

Finally, acute fasting may also increase retrograde synaptic enhancement – at least, based on one preliminary study in the fruit fly (drosophila melanogaster) [59].

18) Exercise May Stimulate Synaptic Plasticity

In both humans and mice, exercise has been associated with increased BDNF, which helps stimulate neurogenesis in the hippocampus, as well as stimulates synaptic plasticity throughout the brain [60].

According to one animal study in rats, long-term exercise (~2 months) seemed to be necessary for the generation of new neurons and sustained increase in synaptic plasticity [61].

19) Serine May Improve Synaptic Plasticity

D-serine is a compound that binds with and activates NMDA receptors, which are believed to play a central role in stimulating synaptic plasticity [62].

In astrocytes (a type of glial cell that performs cellular maintenance to help maintain overall brain health), L-Serine (the natural form of serine) can be converted into D-Serine by the enzyme called serine racemase [62].

About the Author

Nattha Wannissorn

Nattha Wannissorn

PhD
Nattha received her Ph.D. in Molecular Genetics from the University of Toronto and her undergraduate degree in Molecular and Computational Biology from the University of Pennsylvania.
Aside from having spent 15 years in biomedical research and health sciences, Nattha is also a registered holistic nutritionist, a certified personal trainer, has a precision nutrition level 1 certification, and is a certified functional diagnostic nutrition practitioner. As a holistic practitioner with a strong science background, Nattha is an advocate of science literacy in health topics and self-experimentation.

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