Nerve growth factor, also shortened as NGF, owes its impressive nootropic potential to its ability to assist the survival, maintenance, and growth of neurons including cortical neurons, cholinergic neurons, and other factors that promote brain function and power.
Yet, this important nootropic hasn’t really gained the massive appeal as its other nootropic peers, primarily due to a lack of human data.
Here we will look at what nerve growth factor can do for your brain and how it may affect long-term improvements in cognitive function including memory and learning.
What Is A Nerve Growth Factor?
Nerve growth factor (NGF) is a neuropeptide or protein belonging to a class of molecules called neurotrophins.
Neurotrophins are responsible for regulating the growth, development, maintenance, and survival of nerve cells that are associated with important cognitive functions.
In other words, NGF is all about survival and PCD mechanisms or programmed cell death which is a natural phenomenon.
Programmed cell death occurs to eliminate unwanted cells or those that may become potentially dangerous to the rest of the organism. It is a crucial process as not only does it eliminate damaged or abnormal cells, but also defends against infections.
Importance Of Nerve Growth Factor
NGF is considered essential for the cell survival of sensory and sympathetic neurons in the brain.
The NGF gene provides instructions for making this protein, which plays a crucial part in brain health and cognitive function by producing new nerve cells, maintaining the developed ones, and preventing the onset of brain disorders in old age.
NGF production takes place naturally in the body including the frontal cortex, hippocampus, pituitary glands, and the spinal cord.
But even when produced naturally by the body, the amount of naturally occurring NGF can easily vary from one person to the next.
In instances where there are low NGF levels, you can take certain steps to increase NGF production to treat and prevent health complications.
For instance, many modern-day diseases including metabolic syndrome, obesity, type 2 diabetes, and atherosclerosis are linked to low levels of nerve growth factor.
But just as low levels can bring about certain health issues, high levels are also linked to a number of histamine-producing mast cells and different autoimmune diseases.
That’s why it’s important to maintain optimal levels to prevent overstimulation and inflammation.
The Working Mechanism Of Nerve Growth Factor
NGF, being a key neurotrophin, plays an important part in brain growth, development, and longevity. As such when NGF activity is less than optimal in the brain, general cognition suffers.
In the capacity of a neuropeptide, NGF triggers neuronal activity by binding to different NGF receptors.
This mechanism helps promote neurogenesis alongside the following functions:
Modulates Synaptic Plasticity
This refers to the strengthening of the neuron to neuron communication.
Often seen in the hippocampus, nerve growth factor modulation of synaptic plasticity is essential to hippocampal long-term potentiation (LTP). This is a process by which synaptic connections between neurons strengthen with frequent activation.
With an imbalance in NGF levels, hippocampal plasticity, which affects memory and learning, decreases. This indicates the importance of nerve growth factor to the growth and maintenance of memory processing neuronal activity.
Maintains Sympathetic And Sensory Neurons
This improves the connection between sensory peripheral nerves and the central nervous system to improve sensory perception in an individual.
Sensory neurons are responsible for transporting information from the sense organs to the central nervous system. This is an important mechanism without which it would be easy to bite your tongue unknowingly without feeling pain or touching a hot surface.
These neurons are triggered by physical and chemical inputs from the environment making you aware of your surroundings.
Regulates The Immune System
NGF possesses both a pro and anti-inflammatory response depending on the receptor site of activation. As nerve growth factor activates certain inflammatory immune responses, it also lowers other responses, that could otherwise damage the inflamed tissues.
Research is increasingly looking into its role as a key mediator between the immune and nervous systems as it can influence both immune cell activity as well as neuronal cell function.
It’s important to remember that NGF levels decline naturally with age affecting several aspects of brain function. Animal studies show that NGF signaling alters in the aging brain which can contribute to age-related decline in cognitive performance. [*]
Nerve Growth Factor For Cognitive Functions
The nerve growth factor seems to be particularly beneficial for the aging demographic, especially those suffering from age-related cognitive decline.
That being said, it is still found to be beneficial for healthy adults as well in the following cognitive functions:
Memory Retention
Nerve growth factor has been seen to enhance cognition in the areas of memory and learning by improving synaptic plasticity.
NGF gene therapy has been used in clinical trials using animal models of adult rats. Findings show that when NGF levels were blocked, there was a significant difference in the reduction of hippocampal LTP and impaired retention of spatial memory. [*]
Stress-Related Repair
Nerve growth factor plays a part in potentially repairing tissue damage caused by chronic or even acute stress. [*]
More recent studies have looked into the effects of psychological, lifestyle, and oxidative stress on the increased risk of mental disorders and how nerve growth factor activity may impact mental and metabolic disorders related to stress.
Attention And Motivation
NGF supports the survival and structure of cholinergic neurons associated with attention, arousal, and motivation which may indirectly improve attention-related cognition.
Cholinergic neurons provide the primary source of acetylcholine to the brain from where acetylcholine signaling then underlies specific aspects of cognitive functions and behaviors such as attention, learning, memory, and motivation.
May Treat Depression
Some research indicates that participants with higher NGF levels presented a lower rate of major depressive disorder than control subjects.
One recent study suggested that either up or downregulation of nerve growth factor signaling could be a potential prospect for antidepressant treatment. [*]
Other Benefits Of NGF
Alongside cognitive benefits, nerve growth factor may also potentially offer the following benefits:
Lowers Inflammation
Tests utilizing models of the human brain showed that NGF lowered inflammation and promoted the growth of the myelin sheath while repairing the damage.
These findings are promising in the areas of inflammatory brain diseases such as multiple sclerosis, Alzheimer’s disease, and Parkinson’s disease.
Multiple sclerosis involves t-cells interacting in the periphery and central nervous system that contribute to the disease. The condition involves inflammation which is sustained by autoreactive t-cells directed against components of myelin.
Alzheimer’s disease, on the other hand, is a neurodegenerative disorder occurring more frequently in the elderly population.
Promotes Heart Health
Testing done on mice shows that treatment with nerve growth factor regenerated damaged nerves around the artery and blood vessels leading to the formation of new blood vessels.
Researchers believe that NGF treatment is integral to the healing process and may play a greater role after a heart attack or any kind of major heart damage.
May Promote Pancreatic Health
Research shows that NGF is necessary to maintain the health of pancreatic beta cells.
Some limited evidence suggests that pancreatic beta cells express the two NGF receptors TrkA and p75NTR.
Since the elimination of NGF induces apoptosis in pancreatic beta cells, it is assumed that nerve growth factor plays an important part in the survival and maintenance of pancreatic cells.
It May Be Useful For Cancer Prevention
NGF may play a part in preventing the spread of specific types of cancer cells.
It has been noted that when combined with regular administration of vitamin A, nerve growth factor diminishes the growth of hypothalamic or pituitary tumors.
It also seems to slow the growth of lung cancer of the small cell variety.
May Enhance Fertility
Also referred to as an ovulation-inducing factor, NGF is believed to play an important role in female fertility.
The term ovulation-inducing factor refers to its ability to assist the release of the egg from the ovaries of female mammals.
Research shows that insufficient NGF in the follicular fluid results in not only the inability to deliver egg cells but is also linked to higher chances of endometriosis.
It also seems to play an equally important part in male fertility as NGF is believed to be abundant in semen, but its function there remains undetermined. Some theories do suggest that it may increase sperm survival but more research in this area is needed.
When there may be an imbalance of nerve growth factor, NGF boosting supplements can be used to boost levels.
Boosting NGF With Supplements
There are several natural nootropics that can increase NGF safely and without causing side effects.
These supplements are a convenient option to boost NGF in the blood flow to induce and stimulate its production.
Along with cognitive benefits, there is evidence of improving emotional control, mood, and motivation associated with optimal NGF levels.
Nootropics For Nerve Growth Factor
NGF levels may be regulated by using certain nerve growth factor boosting supplements.
Lion’s Mane Mushroom
Lion’s mane is an edible mushroom known to produce NGF.
It is also considered a better option than orally consuming nerve growth factor as NGF has a hard time crossing the blood-brain barrier. The bioactive compounds in Lion’s mane are light enough to reach the brain easily where they activate NGF synthesis and release.
Lion’s mane-related NGF production seems to improve synaptic plasticity associated with learning and memory.
Some research also suggests that using a lion’s mane protects the brain against irregular peptide-induced impairments.
To sum up, lion’s mane is highly recommended for mild cognitive impairments with long-term neuroprotective benefits.
Pyrroloquinoline Quinone (PPQ)
Another popular nootropic to increase nerve growth factor is PPQ.
When administered to promote NGF production, it is believed to help optimize mitochondrial output, reduce free radical damage and resist the build-up of amyloid plaque.
Collectively, these mechanisms are great for promoting brain energy naturally as opposed to flooding the brain with excitatory chemicals.
Animal research indicates that using PPQ could be more effective at increasing NGF signaling without causing cytotoxicity or adverse effects. [*]
Phosphatidylserine (PS)
Often administered for memory and the repair of brain cells, PS is a natural phospholipid crucial for the structural integrity and health of cell membranes.
Among its primary functions, PS is known to stimulate the release of dopamine, increase the production of acetylcholine, improve brain glucose metabolism, lower cortisol levels and boost NGF activity that oversees the health of cholinergic neurons.
Research indicates PS slows and even reverses the decline of learning, mood, memory, and concentration related to dementia or age-related cognitive function.
ALCAR
Typically taken to improve energy levels and muscle strength, acetyl-l-carnitine (ALCAR) has also been used to help with cholesterol and nerve pain.
Some people have also used it to stop cell damage and limited animal research points to its preventive potential associated with aging in the central nervous system. [*]
Some studies claim it increases NGF levels and affects nerve regeneration in rats. [*]
Quercetin
Quercetin is a plant flavonoid with antioxidant and anti-inflammatory properties. Its purported benefits include a reduction in swelling, killing cancer cells, regulating blood sugar, and preventing heart disease.
Studies show quercetin to prevent further cell damage when administered with NGF in animal models. [*]
Quercitin treatment also shows promising potential for nerve growth with the ability for peripheral nerve regeneration. [*]
Noopept
Animal studies show Noopept to stimulate both NGF and BDNF expression in the hippocampus.
According to one rat study, a 28-day administration of Noopept revealed significant increases in neurotrophic factors in the hippocampus. [*]
Green Tea Extract
Green tea provides users with two compounds of interest that can potentially increase NGF.
The first is l-theanine which seems to yield green tea’s greatest mental advantage of enhancing alpha brainwave activity.
In addition, according to one study, when administered to rats, it increased LTP and NGF activity in the hippocampus as compared to placebo. [*]
The second is EGCG whose polyphenol content works synergistically to increase NGF. [*]
Vitamin D
Limited research on vitamin D indicates that it prevented beta-amyloid-induced calcium toxicity and elevation that targets NGF release in neurons.
Result findings from the study indicated that vitamin D regulated NGF release that helped the survival of both cortical and hippocampal neurons.
Side Effects Of Nerve Growth Factor
NGF needs to be present in optimal amounts to offer the most health benefits. Either too much or too little can cause health concerns and present problematic side effects.
Increased Chronic Pain
For instance, in the process of inflammation, NGF gets released in high concentrations by mast cells and induces axonal growth in nearby nociceptive neurons. This can lead to increased pain perception in inflammatory regions. [*]
Likewise, high NGF levels are often observed in several, though not all, patients with chronic pain.
Cancer Progression
NGF may also stimulate the spread and promote cell survival of tumors.
While NGF can assist in repair and healing by inducing the active form of cell reproduction in the body, too much may also cause cancerous cells to multiply.
Given the rapid cell growth associated with NGF, new blood vessel production also speeds up which may make it hard to remove cancer tumors.
Autoimmune Diseases
In the instance of autoimmune disorders, an overproduction of NGF affects the immune and nervous systems along with the hormonal system causing further damage.
Typically, doctors will follow an anti-NGF treatment to lower the production of NGF and manage the illness.
Schizophrenia
Even though there is evidence of NGF being helpful for conditions like Alzheimer’s disease and dementia, research shows it to be a possible factor in developing schizophrenia given the change it causes in blood levels.
While some studies associate decreased blood levels with an increased risk of schizophrenia, others link it to higher NGF and BDNF levels in schizophrenic patients.
Limitations Of Using Nerve Growth Factor
NGF, without doubt, is integral to the proper functioning of the nervous system and all cognitive pathways. However, most of this evidence comes from studies on lab animals with very little research involving human participants.
Further studies are needed to establish these benefits transferring to humans.
Verdict
Even though it is considered most beneficial for the aging population, there is no doubt that the nerve growth factor is good for overall brain health and memory at any age.
It covers all aspects of neurogenesis, neuroprotection, and comprehensive brain optimization.
It is possible to use standalone supplements that enhance the production of NGF or get a premade stack to do the job instead.