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. To prevent or mitigate the effects of any neurodegeneration, strategic administration of a neuroprotective agent may be beneficial.
Administration of a neuroprotective agent may help minimize the effects of chronic conditions that could: kill brain cells, decrease brain volume, and lead to long-term functional impairment. Specific examples of things that can cause neurodegeneration include: traumatic brain injuries, drug abuse, pharmaceutical medications, schizophrenia, strokes, and dementia. For this reason, many people have turned to neuroprotective agents in hopes that they will help preserve long-term mental health.
Neuroprotective Agents: List of Drugs & Supplements
There are different types of neuroprotective agents, some of which help reduce glutamate-induced excitotoxicity, while others that reduce oxidative stress. The most common cause of neurodegeneration is oxidative stress, therefore considering neuroprotective agents may be beneficial for long-term brain health.
- AC-11: This is a substance that is found in various nootropic formulations and may help with enzymatic repairs. It is 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: This is a naturally occurring substance that has been shown to elicit neuroprotective effects in animal models following a stroke. It is hypothesized that the “acetyl” component helps reduce oxidative damage and brain lactate levels. The substance demonstrated an ability to pervent excitotoxicity as well as reduce oxidative stress markers throughout the brain and spinal fluid. Further research is necessary to fully understand whether acetyl-L-carnitine promotes neuroprotection in humans.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16179519
- Acetylcholinerase inhibitors: This class of drugs functions by inhibiting the neurotransmitter acetylcholinerase, which can improve brain performance. Many are used to help decrease neurodegeneration associated with Alzheimer’s disease. They can help decrease neurotoxicity as a result of glutamate and prevent neuronal death.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16762377
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19714494
- Acetylcysteine: This 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 (with varying degrees of success) 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.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23369637
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23178231
- Anti protein aggregation agents: The aggregation of protein can lead to the death of neurons. Various treatments are being developed to function as anti-protein aggregation agents, thus preventing neurodegeneration. Examples include: sodium 4-phenylbutyrate, trehalose, and polyQ-binding peptide.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19560879
- Bacopa monnieri (BM): This herb has a variety of medicinal proeprties and is hypothesized to have neuroprotective effects. It is 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. It is believed that this herb may help prevent cognitive decline associated with Alzheimer’s disease.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22700087
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19808086
- Caffeine: This is perhaps the most widely-used neuroprotective substance and has been shown to help protect the brain against development of Parkinson’s disease. It also is capable of increasing the uptake of cysteine, which leads to glutathione synthesis, inevitably resulting in neuroprotective effects.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11772120
- Cannabinoids: 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.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10863546
- Caspase inhibitors: This class of drugs is regarded as having neuroprotective benefit primarily as a result of their ability to prevent the death of neurons. It is thought that these drugs may help mitigate certain neurodegenerative aspects of diseases like Parkinson’s.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15935070
- Citicoline (CDP-Choline): This substance 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. The fact that it helps synthesize SAMe tends to lower the amount of arachidonic acid in the brain, which can be helpful following a stroke.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11796739
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10561698
- Crocin: This is a compound that is commonly found in the plants gardenia and crocus, and comprises the color “saffron.” It is 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.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17090119
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17215084
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17274961
- Curcumin: Although some argue that curcumin is regarded as having poor bioavailability when taking orally, it is known 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.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527619/
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24004419
- 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.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11259643
- Estrogen: 17-beta estradiol is known to act as an antioxidant with neuroprotective effects. Although there isn’t much research surrounding the usage of estrogen as a neuroprotective agent, benefits have been discovered in rodent studies. It was found to prevent damage from oxidative stress and DNA degredation. Further research is needed to confirm any speculation of neuroprotection in humans. In addition to the aformentioned 17-beta estradiol as a neuroprotective agent, 17-alpha estradiol also provides neuroprotection. It tends to act as a potent antioxidant and help prevent cell death in neurodegenerative disorders like Alzheimer’s disease.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9106616
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7488136
- Fish oil: Within fish oil are n-3 PUFAs (polyunsaturated fatty acids), which 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.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22289576
- Ginsenoside Rd: This 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. This is a substance that has been studied in humans, and is 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. Greatest neuroprotective benefit for stroke victims was derived from taking 50 mg/kg.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23738998
- L-Theanine: This is an amino acid analogue that is derived primarily from green tea. When supplemented with caffeine, L-theanine appears to help increase IQ. It is speculated that L-theanine has some neuroprotective properties. In rat studies, L-theanine administration following a stroke significantly decreased the area of damage. This substance appears to minimize any damage resulting from glutamate receptor agonists.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23097345
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21477654
- Lithium: Various compounds of lithium are utilized to treat psychiatric conditions such as bipolar disorder. They tend to stabilize the mood and tend to inhibit the transition from a depressive state into mania. Some studies have discovered that lithium acts as a neuroprotective agent, decreases inflammation, improves mitochondrial function, and promotes neurogenesis among cases of traumatic brain injuries.
- Source: http://pubs.acs.org/doi/abs/10.1021/cn500040g
- Melatonin: 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. A study conducted in cats found that melatonin provided significant neuroprotection following a stroke.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19196437
- Source: http://www.sciencedirect.com/science/article/pii/S0188440901002685
- Minocycline: This is an antibiotic of the tetracycline classification that is long-acting and contains significant antioxidant properties. It has been shown to offer neuroprotective benefit in mouse models of neurodegenerative disorders such as: Huntington’s, Parkinson’s, and Alzheimer’s. It may also help to minimize symptoms of schizophrenia and decrease inflammation.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17239606
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19895780
- Nicotine: In both human and monkey studies, nicotine has been shown to delay the onset of Parkinson’s disease. In rodent studies, nicotine administration resulted in protection of neurons from glutamate-induced neurotoxicity. The nicotine inhibited neuronal death in the cortex of rodents.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19714494
- Noopept: This 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.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12596521
- Source: http://www.sciencedirect.com/science/article/pii/S0022283611010849
- Source: http://www.jbiomedsci.com/content/21/1/74
- PQQ (Pyrroloquinoline quinone): This is 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.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8401318
- Source: http://www.ncbi.nlm.nih.gov/pubmed/18591768
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20083898
- Progesterone: This is a steroid hormone that is naturally produced by the body and is commonly referred to as “P4.” It functions to aid in the process of menstruation and pregnancy, but also functions in the brain as a neurosteroid. Those that suffer from traumatic brain injuries and strokes are thought to benefit from supplementation of progesterone. Animal research clearly demonstrates that progesterone provides neuroprotection immediately after a brain injury, and small-scale human studies had similar findings. This hormone is also thought to have synergistic neuroprotective effects when co-administered with Vitamin D.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17715141
- Source: http://www.ncbi.nlm.nih.gov/pubmed/18447940
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19394357
- Resveratrol: This is a substance that is naturally produced by plants and is commonly known as being found on the skin of blueberries, grapes, and raspberries. Some studies have shown that it is capable of inhibiting oxidative stress as a result of reactive oxygen species. Limited research supports the idea that it may be neuroprotective in cases of Alzheimer’s, Parkinson’s, strokes, and other CNS disorders.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21208792
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16766037
- Selegiline: This drug is an MAOI that tends to inhibit MAO-B, resulting in improvement in cognitive deficits associated with Parkinson’s disease. The drug increases neuronal survival and is capable of protecting neurons against an array of neurotoxins. It also decreases oxidative radicals and helps promote healthy neurotransmission.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11813232
- Simvastatin: This is a drug most commonly known as “Zocor” and is used to decrease high lipid levels as well as heart problems. In mouse studies, administration of this drug has been shown to have neuroprotective effects as a result of its ability to modulate NMDA (glutamate) receptors. It also tends to decrease inflammation. Determining whether the neuroprotective benefits are applicable to humans warrants additional investigation.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22492045
- Targeted hypothermia: This is known as a treatment that modifies a person’s body temperature in effort to improve mental health. Those that suffer a stroke or brain injury may use this protocol in order to decrease the likelihood of injury resulting from decreased blood flow. It is believed that it: reduces free radicals (that could damage the brain), decreases levels of glutamate, minimizes intracranial pressure, and decreases the brain’s oxygen demand – thus potentially eliciting therapeutic benefit.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20236503
- Trophic factors: Growth factors function to aid in cellular signaling and are believed to offer some neuroprotective benefit, most notably for those with ALS. Examples of trophic factors being investigated for potential neurprotective effects include: BDNF, CNTF, IGF-1, VEGF. While there is a shortage of human studies regarding neuroprotection from trophic factors, there is clear benefit in rodents.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19109933
- Vinpocetine: This is a synthetic drug that is derived from the periwinkle plant. It is known to increase blood-flow to the brain and is believed to elicit neuroprotective effects. It 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. The drug also has significant anti-inflammatory properties, which likely promotes neuroprotection.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23121080
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22874716
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12044859
- 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 is believed to act as an antioxidant, reducing the amount of oxidative stress within the brain. When investigated as a neuroprotective agent among individuals with Parkinson’s disease, it was found ineffective. That said, it is believed to help prevent neurodegeneration associated with stroke and glutamate.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16166580
Benefits of Neuroprotective Agents
There are many benefits that can be obtained from the usage of neuroprotective agents. Most people use them as a means of improving brain function following an injury, but they may also be utilized to delay onset of a neurodegenerative disorder.
- 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 preexisting 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: There is evidence that many of these neuroprotective agents help improve mitochondrial function. 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. The accumulation of neurotoxins over an extended period of time can kill brain cells, and impair functioning. Many of the substances listed above directly act to prevent damage as a result of various neurotoxins.
Who should use neuroprotective agents?
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: An array of neurodegenerative disorders such as ALS and dementia clearly are able to derive benefit from neuroprotective agents. Certain substances like Selegiline have been shown to significantly delay onset of neurodegeneration and are frequently prescribed. It is important to realize that some neuroprotective drugs tend to work well for some disorders (e.g. Parkinson’s), but may worsen others (e.g. ALS).
- Schizophrenia: 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.
Bottom line: Determining “best” neuroprotective agent is subject to variation
It is important to realize that certain neuroprotective agents are suited for specific conditions. Therefore shoveling down the entire laundry list of neuroprotective drugs and supplements listed above may lead to more unwanted side effects than therapeutic ones. Always double check with a professional before assuming that your specific condition warrants a particular drug for neuroprotection.
Also understand that although certain neuroprotective drugs may help preserve brain health, they do not come without risk of long-term effects. Most individuals that suffer any sort of condition that leads to neurodegeneration are already taking proper medications to help provide neuroprotection. In upcoming years with advances in technology and medicine, it is hoped that more effective neuroprotective agents are discovered to possibly decrease or reverse neurodegeneration in the human brain.
If you are taking any of these substances for the particular purpose of neuroprotection, or know anyone that is, feel free to share a comment below regarding the experience. Also if you know of a particular neuroprotective agent that wasn’t mentioned within this article, be sure to share it along with a link to a study demonstrating its effect.