Could Coffee Be the Best Nootropic? (It’s Not The Caffeine!)



Neuroprotective Compounds in Coffee


A new study from Rutgers University reports that caffeine plus another compound found in the waxy coating of coffee beans may help protect the brain against Parkinson’s disease.


Rutgers scientists have found a compound in coffee that may team up with caffeine to fight Parkinson’s disease and Lewy body dementia – two progressive and currently incurable diseases associated with brain degeneration.



More Than Just Caffeine

The discovery, recently published in the Proceedings of the National Academy of Sciences, suggests these two compounds combined may become a therapeutic option to slow brain degeneration.

Lead author M. Maral Mouradian, director of the Rutgers Robert Wood Johnson Medical School Institute for Neurological Therapeutics and William Dow Lovett Professor of Neurology, said prior research has shown that drinking coffee may reduce the risk of developing Parkinson’s disease.

While caffeine has traditionally been credited as coffee’s special protective agent, coffee beans contain more than a thousand other compounds that are less well known.


The Key is in the Bean’s Waxy Coating

EHT in the bean’s waxy coating protects against Parkinson’s and Lewy body dementia.

The Rutgers study focused on a fatty acid derivative of the neurotransmitter serotonin, called EHT (Eicosanoyl-5-hydroxytryptamide), found in the bean’s waxy coating.

The researchers found that EHT protects the brains of mice against abnormal protein accumulation associated with Parkinson’s disease and Lewy body dementia.

In the current research, Mouradian’s team asked whether EHT and caffeine could work together for even greater brain protection. They gave mice small doses of caffeine or EHT separately as well as together.

Each compound alone was not effective, but when given together they boosted the activity of a catalyst that helps prevent the accumulation of harmful proteins in the brain.


This suggests the combination of EHT and caffeine may be able to slow or stop the progression of these diseases.


This is particularly exciting news, because current treatments address only the symptoms of Parkinson’s disease but do not protect against brain degeneration.

Mouradian said further research is needed to determine the proper amounts and ratio of EHT and caffeine required for the protective effect in people.

“EHT is a compound found in various types of coffee but the amount varies. It is important that the appropriate amount and ratio be determined so people don’t over-caffeinate themselves, as that can have negative health consequences,” she said.

According to the U.S. Department of Health & Human Services, Parkinson’s disease is a brain disorder that can lead to shaking, stiffness and difficulty with walking, balance and coordination. Nearly one million people in the United States are living with Parkinson’s disease.

Lewy body dementia, one of the most common forms of dementia, affects more than one million people in the United States. It causes problems with thinking, behavior, mood, and movement.


Neuroprotective Agents

Neuroprotective agents refer to substances that are capable of preserving brain function and structure.

When the brain is exposed to high levels of oxidative stress, mitochondrial dysfunction, inflammation, various forms of neurotoxicity (e.g. excitotoxicity), and protein deficiencies – neurodegeneration can occur.


Benefits of Neuroprotective Agents


Brain Activity



Many neuroprotective agents alter brain activity and improve health in regions that have become impaired. For this reason, they are often utilized to improve function following a traumatic brain injury.

Anyone that has suffered some form of stroke and/or been diagnosed with a neurodegenerative disorder will likely take steps in attempt to normalize their brain activity – some of which may involve taking neuroprotective agents.


Cognitive Function



Certain agents are capable of improving cognition and mental performance in pre-existing cases of neurodegenerative diseases.

Memory and attentional processes tend to decline as the neurodegeneration escalates, but can often be corrected with proper administration of a neuroprotective agent.


Mitochondrial Function


Mitochondria are the “powerhouse” of the cell.


There is evidence that many of these neuroprotective agents help improve mitochondrial function (mitrochondia are the “powerhouse” of the cell).

Mitochondria are responsible for powering neurons, regulating their energy and helping them survive.

They help improve signaling between neurons and healthy functioning can help prevent certain aspects of neurodegeneration.


Neurotransmitter Function


Some of the neuroprotective agents listed above improve efficiency and functioning of various neurotransmitters throughout the brain.

Healthy neurotransmitter function can improve neuronal health and mitigate neurotransmitter deficits resulting from neurodegeneration.


Reducing Neurotoxicity

Neurodegeneration often occurs as a result of elevated levels of neurotoxins, and the accumulation of neurotoxins over an extended period of time can kill brain cells, and impair functioning.


Should You Use a Neuroprotective Agent?



There are many individuals that stand to benefit from taking a neuroprotective drug and/or supplement stack.

Below are some examples of groups that would likely benefit from a neuroprotective substance.


Age-Related Cognitive Decline

Much of the cognitive decline associated with aging can be slowed or mitigated with the right neuroprotective agent and/or combination.

Nearly everyone experiences age-related cognitive decline, but some experience it at a much younger age. Those with early-onset decline may get the most benefit.


Neurodegenerative Disorders

Many neurodegenerative disorders such as Parkinson’s, ALS and dementia can benefit from neuroprotective agents.


Neurodegenerative Disorders


Detailed information on specific neurodegenerative disorders can be found at the NIH – National Institute of Neurological Disorders and Stroke.



There is some evidence supporting the idea that certain neuroprotective drugs may provide benefit in reducing neurological damage and cognitive symptoms of the disease.


Stroke Victims

Most studies in support of neuroprotective substances are in regards to repairing neurological function after an ischemic stroke.

Stroke victims suffer a significant degree of impairment, but with proper medical intervention (often with these drugs), a person can considerably improve brain health and functioning.


Viral-Related Neurodegeneration

Many cases of individuals diagnosed with viral infections such as HIV/AIDs tend to experience neurodegeneration and neurological deficits.

In some cases, it may be beneficial to utilize a particular neuroprotective agent and/or supplement to help minimize damage.


Promising Neuroprotective Agents


A neuroprotective or disease-modifying therapy nay slow or stop disease progression and prevent the development of intolerable disability.



This is a substance that is found in various nootropic formulations and may help with enzymatic repairs.  It’s believed to help protect against DNA damage and reduce the likelihood of cognitive decline.

The true neuroprotective aspects of this particular substance are speculative and scientific research is needed to verify any touted benefit.



Acetyl-L-carnitine is a naturally occurring substance that has been shown to elicit neuroprotective effects in animal models following a stroke.

It ‘s hypothesized that the “acetyl” component helps reduce oxidative damage and brain lactate levels. It has demonstrated an ability to prevent excitotoxicity and reduce oxidative stress markers throughout the brain and spinal fluid.


Acetylcysteine (NAC)

Acetylcysteine is both a supplement and pharmaceutical drug that is utilized mostly to decrease mucus build-up, but is also sometimes used for overdose of acetaminophen.

Additionally, it has been used to treat various psychiatric conditions such as OCD, schizophrenia, and various addictions.

This substance is derived from “cysteine” and is thought to offer neuroprotective benefits as a result of: glutamate modulation, its antioxidant effect (glutathione), and mitochondrial enhancement.


Bacopa Monnieri (BM)

Bacopa Monnieri has a variety of medicinal properties and is hypothesized to have neuroprotective effects.

Bacopa Monnieri is also known as “Brahmi”, after Brahmā, the creator God of the Hindu pantheon.

It’s known to improve cognitive function and some studies have found that it is able to reverse memory impairment in rodents.

Administration of BM results in significantly less oxidative damage and restores function of antioxidant enzymes, and may help prevent cognitive decline associated with Alzheimer’s disease.



Caffeine protects the brain against Parkinson’s disease and other neurodegenerative diseases.


Caffeine is perhaps the most widely-used neuroprotective substance and has been shown to help protect the brain against development of Parkinson’s disease.

It’s also capable of increasing the uptake of cysteine, which leads to glutathione synthesis, inevitably resulting in neuroprotective effects.




In some rodent studies, various cannabinoids were found to have neuroprotective properties. Particularly it was found that THC and cannabidiol both reduced levels of NMDA and AMPA induced neurotoxicity.

This suggests that the cannabinoids may have some antioxidant benefits and protect the brain from glutamate-based neurotoxicity.

Further evidence needs to be collected before we assume the same in humans.


Citicoline (CDP-Choline)

Citocoline is derived from choline and is documented as being able to increase density of dopamine receptors in the brain.

It has a clear nootropic effect and has potential to improve both attention and mental energy.

Supplementation may improve mitochondrial functioning and neuronal processes, thus decreasing the likelihood of neurodegeneration.

Cotocoline helps synthesize SAMe tends to lower the amount of arachidonic acid in the brain, making it particularly helpful following a stroke.



Example: IPro Saffron Extract

Crocin (marketed as a Saffron supplements) is a carotinoid commonly found in the plants gardenia and crocus, and is responsible for the color in saffron.

It’s believed to act as a very potent neuroprotective antioxidant via the presence of its sugars.

There is even some research to suggest that it may also have a very slight antidepressant effect in both rodents and humans:

Study Sources:





Although some argue that curcumin is regarded as having poor bioavailability when taking orally, it is proven to have many neuroprotective benefits.

In both animal and cellular models, curcumin is believed to help prevent and/or treat neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and stroke.

One study found that it reduces amyloid-beta membrane toxicity (resulting from calcium ions) among those with Alzheimer’s disease.

Taking curcumin with black pepper (or bioperine) has shown to improve its absorption.


Erythropoietin (EPO)

This is a cytokine hormone that is responsible for the production of red blood cells.

Studies in rodents have demonstrated that by administering EPO, it can effectively inhibit cerebral hypoxia (or lack of oxygen in the brain).

Whether a similar administration would prove beneficial for human stroke victims warrants investigation. It should also be mentioned that EPO may help enhance memory functions.


Fish Oil


Within fish oil are n-3 PUFAs (polyunsaturated fatty acids), which are proven to work to significantly dampen oxidative stress and increase health of mitochondria in rodents.

While it hasn’t been verified as to whether these same benefits can be derived from human consumption of fish oils, many speculate that they can.

Further investigation is needed to understand whether fish oils are capable of preserving neural function in humans.

On a personal note,  I’m convinced, through my research of this and many other blog posts, that fish oil supplements are worth taking daily, for a whole host of reasons. I take MegaRed Krill Oil, which is a very popular supplement.


Ginsenoside Rd

Ginosenoside Rd comes from the root of the Panax ginseng plant.

Ginosenoside Rd is a substance derived from the root of the ginseng plant (Panax). This is one of many compounds that isn’t well understood because they tend to elicit effects upon many different pathways within the cortex.

In humans, Panax ginseng has been shown to prevent glutamate-induced excitotoxicity. It also was tested in clinical trials and discovered to be highly neuroprotective for those who had suffered an ischemic stroke.



L-Theanine is an amino acid analogue that is derived primarily from green tea. When supplemented with caffeine, L-theanine appears to help increase IQ.

Caffeine on its own is not a great cognitive enhancer. In fact, studies show that it doesn’t usually improve performance in learning and memory tasks, though its stimulant properties may occasionally have beneficial effects on cognitive performance and mood (though temporarily — what is usually accompanied by jitters and a crash).

Now that said, when consumed in conjunction with L-theanine, a common amino acid found in green tea, it does in fact create more long-lasting and beneficial effects, including a boost to working memory, rapid visual information processing, and especially attention switching (i.e. reduced distractibility).

L-Theanine is a common amino acid found in green tea.

The reason this works is that the L-theanine, which can cross the blood-brain barrier, counteracts the negative stimulant effects of caffeine, including anxiety and increased blood pressure.

Researchers have found that this effect can be achieved with 50 mg of caffeine (that’s about a cup of coffee) and 100 mg of L-theanine (green tea only contains about 5-8 mg of it, so you’ll want to supplement — though some people follow a 2:1 rule in which they drink two cups of green tea for every cup of coffee).



This is a hormone that helps the body regulate its sleep-cycle. When supplemented, it has been thought to have neuroprotective effects as a result of its ability to reduce free radicals in the brain.

Free radicals are known to contribute to various forms of brain damage, therefore reducing the quantity could improve mental performance.

Studies have found that melatonin provides significant neuroprotection following a stroke.

Melatonin is also a powerful antioxidant, which may provide a variety of other benefits. In fact, it may help support eye health, treat stomach ulcers and heartburn, ease tinnitus symptoms and even raise growth hormone levels in men.


Read: The Complete Guide to Better Sleep With Melatonin



Noopept is a peptide most commonly found in Russia as a nootropic. It provides benefit by acting as an antioxidant, decreasing inflammation, and prevents neurotoxicity resulting from calcium and/or glutamate. There is also some evidence suggesting that this substance helps reduce cytotoxicity as a result of various forms of dementia and prevents neuronal death.

In test tube-based studies, Noopept was neuroprotective and prevented cell death from amyloid toxicity, which is the cause of Alzheimer’s and Parkinson’s symptoms.

A cellular model experiment found that Noopept also prevents oxidative damage and mitochondrial cell death, important for fighting Alzheimer’s and Parkinson’s diseases.


PQQ (Pyrroloquinoline Quinone)

Pyrroloquinoline quinone (PQQ) was first discovered as a cofactor for enzyme reactions in bacteria where it serves a similar function to that of B vitamins for humans.

A “cofactor” just means that it helps enzymes accomplish their jobs. There is a class of these cofactor molecules that transfer electrons, which is important for our mitochondria to produce energy.

It’s considered a redox cofactor in bacteria and has demonstrated potent neuroprotective effects in both animals and humans. In some cases it is capable of reversing cognitive impairment as a result of excess oxidative stress and can also improve memory functions.

Supplementing PQQ is capable of helping with memory function in aging humans as a result of releasing “nerve growth factors.” It is believed to help prevent certain types of Parkinson’s disease, Alzheimer’s disease, as well as damage following a stroke.

Among PQQ’s Many Benefits:

  • Protects against Parkinson’s, Alzheimer’s, and cognitive injuries
  • Reduces inflammation and free radicals
  • Creates new mitochondria
  • Improves memory and reasoning
  • Increases nerve growth factor


How PQQ Protects Brain Function

PQQ increases a protein (DJ-1) that is important to brain health and function. This protein, which increases cell function and survival by combating intensive oxidative stress, is likely important to brain health and function.

DJ-1 mutations have been conclusively linked to the onset of rare inherited forms of Parkinson’s disease and other neurological disorders.

PQQ suppresses reactive nitrogen species (iNOS causes this), which spikes in strokes and brain injuries. In this manner, it provides protection against neuro-related injuries.

In animal models, administration of PQQ immediately prior to induction of stroke significantly reduced the size of the damaged brain area.

PQQ also protects neurons by preventing the long-term overactivation of the NMDA receptors, which results in excitotoxicity. Long-term, overstimulation of neurons is associated with many neurodegenerative

Popular Choice: Jarrow PQQ

diseases and seizure.

It also protects the brain against neurotoxicity induced by other powerful toxins, including mercury and oxidopamine, toxins that are suspected to cause Alzheimer’s and Parkinson’s, respectively.

PQQ also prevents aggregation of alpha-synuclein and amyloid-beta, proteins associated with Parkinson’s and Alzheimer’s diseases, respectively.

It also protects nerve cells from the toxic effects of the proteins that are already there.




Resveratrol is naturally produced by plants and is commonly known as being found on the skin of red grapes, blueberries, and raspberries.

Several studies have suggested that drinking red wine can help slow down age-related cognitive decline.

It seems to interfere with protein fragments called beta-amyloids, which are crucial to forming the plaques that are a hallmark of Alzheimer’s disease.

Additionally, resveratrol may set off a chain of events that protects brain cells from damage.

Lifelong supplementation of resveratrol may increase lifespan and delay biomarkers of Alzheimer’s (by preventing beta-amyloid and tau protein aggregation).



Perriwinkle (Vinca minor)

Vinpocetine is a synthetic drug that is derived from the periwinkle plant. It’s known to increase blood-flow to the brain and is believed to elicit neuroprotective effects, and is commonly used throughout Europe for the treatment of age-related cognitive decline – specifically memory impairment.

Its mechanism of action involves blocking voltage-sensitive sodium channels in the brain, which decreases levels of calcium ions – thus likely minimizing oxidative damage. It also has significant anti-inflammatory properties, which likely promotes neuroprotection.



Improves Cognitive Power

Good Value: WLV Vinpocetine

In one study, patients received either 30 mg of Vinpocetine per day, 60 mg of Vinpocetine per day or a placebo.

After 16 weeks, both Vinpocetine groups had notable improvements in cognitive performance.

There was no significant difference in cognitive benefits between taking 30mg and 60mg per day.


Slows Cognitive Decline

One week of intravenous infusions of vinpocetine, followed by 90 days of 30mg oral dosage, significantly improved the symptoms of cognitive decline in individuals with poor blood circulation in the brain. For example, physical balance was markedly improved.


Improves Mitochondrial Function

Vinpocetine reduces the loss in mitochondrial membrane potential (needed to create ATP) caused by excitotoxicity (when neurons are damaged and killed by the overactivations of receptors for the excitatory neurotransmitters).

Similarly, at high blood levels, Vinpocetine is able to reverse the decrease in mitochondrial function seen with beta-amyloid pigmentation.


Vitamin E

Popular Example: Puritan’s Pride Vitamin E

Although abnormally high levels of Vitamin E are thought to produce detrimental health effects, some evidence suggests that Vitamin E is capable of providing neuroprotection.

It’s believed to act as an antioxidant, reducing the amount of oxidative stress within the brain.


Patients with Alzheimer’s disease (AD) have been found to have lower levels of vitamin E in the cerebrospinal fluid that nourishes and protects the brain.


What to Read Next


0 0 vote
Article Rating
Notify of
Inline Feedbacks
View all comments
Would love your thoughts, please comment.x