NGF: What is Nerve Growth Factor and 60+ Ways to Increase It (And What To Avoid)

Nerve Growth Factor

NGF has been shown to have roles in development of the male and female reproductive systems, the endocrine, cardiovascular and immune systems. R

 
 

Basics

Nerve Growth Factor (NGF) is a protein in a group called neurotrophins (like BDNF, CNTFGDNF, CDNF, and MANF) that increases neurogenesis. R

Nobel Laureates Rita Levi-Montaclini and Stanley Cohen first isolated NGF in 1956. R

Rita Levi-Montaclini took a daily solution of NGF in the form of eye drops, and stated that her brain was more active in her 100's than it was in her 20's. R

Nerve growth factor may contribute to increased longevity and mental capacity, as Rita lived to age 103. R

Alterations in NGF levels have been implicated in neurodegenerative disorders and psychiatric disorders, such as Alzheimer's disease, Huntington's disease, depression and substance abuse. R

NGF was an average of 194pg/ml, in normal people. It was 112pg/ml in females and 243 pg/ml in males. R 

Low NGF is commonly found in atherosclerosis, obesity, type 2 diabetes, and metabolic syndrome. R

High NGF are found in autoimmune diseases that have increased mast cells, like histamine intolerance. R

Benefits

1. Helps Nerves Regenerate

 
 

NGF promotes peripheral nerve regeneration in rats. R

NGF treatment of superior cervical ganglia neurons results in survival and axonal growth. R

2. Supports Fertility

 
 

NGF is also referred as OIF (Ovulation-inducing factor). R

NGF can induce ovulation in some mammals. R

Low NGF (and BDNF) in ovary follicular fluid may make it harder for ovary's to provide egg cells and is associated with a higher risk of endometriosis. R

3. Promotes Myelin Repair

NGF appears to promote myelin repair. R

4. May Treat Multiple Sclerosis

NGF may be useful for the treatment of multiple sclerosis. R

5. May Improve Psychiatric Disorders

 
 

NGF may help improve dementia, depression, schizophrenia, autism, Rett syndrome, anorexia nervosa, and bulimia nervosa. R

Low levels of NGF have been found in the cerebral spinal fluid of children with Rett syndrome compared to children with Autism who have relatively normal to high levels. R

Decreased NGF may serve as a biological marker when assessing the present state of a bipolar disorder patient. R

When bipolar disorder patients were treated with lithium, their NGF concentrations increased in the frontal cortex, limbic forebrain, hippocampus, and amygdala. R

6. May Help Neurodegenerative Diseases

Nerve growth factor prevents or reduces neuronal degeneration in animal models of neurodegenerative diseases. R

Dysregulation of NGF signaling has also been linked to Alzheimer's disease. R R R R R R

An increase in cortical and subcortical NGF has been found in patients with Alzheimer’s disease. It may be caused by an atypical production or use of receptors in the brain. R

Stimulating NGF receptors via NGF infusion has been shown to increase blood flow and verbal episodic memory, which is longer lasting than other treatments for Alzheimer's. R

7. May Help with Alcohol-Induced Memory Loss

 
 

NGF has been shown to restore learning ability in rats recovering from induced alcoholism. R

8. Helps Accelerate Wound Healing

NGF has also been shown to accelerate wound healing. There is evidence that it could be useful in the treatment of skin ulcers and cornea ulcers. R

9. Helps Survival of Pancreas

There is evidence that pancreatic beta cells express both the TrkA and p75NTR receptors of NGF. R

Withdrawal of NGF induces apoptosis in pancreatic beta cells, signifying that NGF may play a critical role in the maintenance and survival of pancreatic beta cells. R

Diabetic neuropathy may be associated with low levels of NGF in the blood. R

10. May Help Romantic Love

 
 

NGF in the blood plasma is significantly higher in individuals who have been in a romantic relationship with another person for less than 12 months (vs single vs 12+month relationships. R

NGF can indirectly stimulate the expression of ACTH in the HPA by increasing vasopressin secretion. ACTH binds to the MC2 receptor in the Zona fasciculata of the adrenal cortex stimulating secretion of cortisol. R

This rapid increase of cortisol in the blood plasma can induce feelings of euphoria, which may explain the initial "rush" of falling in love. R

11. Repairs and Prevents Heart Problems

NGF helps the heart repair after a heart attack. R

In mice:

  • They replicated an injury to the artery and NGF regenerated the nerve around the blood vessels, helping form new blood vessels by supporting their development and stabilization. R

12. May Prevent Growth of Certain Cancers

 
Signaling pathways activated by nerve growth factor (NGF). NGF binding to TrkA receptor mediates proliferation, differentiation and survival via activation of PI3K/Akt, Ras/MAPK and PLCγ pathways. 

Signaling pathways activated by nerve growth factor (NGF). NGF binding to TrkA receptor mediates proliferation, differentiation and survival via activation of PI3K/Akt, Ras/MAPK and PLCγ pathways. 

 

In hypothalamic or pituitary tumors, NGF prevented the spread of small cell lung cancer cells. Vitamin A enhanced this effect. R

Drawbacks of High NGF

1. May Increase Pain

 
 

In the process of inflammation, NGF is released in high concentrations by mast cells, and induce axonal outgrowth in nearby nociceptive neurons. This leads to increased pain perception in areas under inflammation. R

In acquired immunity, NGF is produced by the Thymus as well as CD4+ T cell clones, inducing a cascade of maturation of T cells under infection. R

In some gynecological diseases, an elevated prostaglandin E2 is thought to stimulate production of NGF which contributes to the perception of pain and increased inflammation in endometriosis. R

NGF expression fluctuation (along with other factors) may help to explain gender differences in pain sensation and inflammation. R

2. Maintains Inflammation

High levels of NGF were associated with chronic inflammation. R

By releasing more NGF in inflammatory conditions, inflammation in cells contribute to the increased NGF levels observed in patients with asthma. R

High levels of NGF are often seen in patients with chronic pain, but not all cases. R

As a part of the inflammatory response, NGF may be higher in brain injury. R R

3. May Contribute to Histamine Intolerance 

 
 

Mast cells can be activated by NGF (unlike BDNF), which may contribute to histamine intolerance. R V

Fortunately, activation of CB2 receptors (like taking CBD) attenuates NGF-induced mast cell degranulation. R

4. May Spread Certain Cancers

NGF (and BDNF) stimulates spread and survival of tumor cells, promoting new blood vessel production in tumors. R

NGF can increase the promotion of gastric cancer, so anti-NGF therapy may be a potential protocol. R

 
 

How to Increase NGF

 
 

 

 

Lifestyle

  • Exercise (and intense exercise like HIST) R R R
  • Love R
  • Social Enrichment (early on in life) R
  • Stress Reduction R R
  • Sun (UV increases it as well) R
  • Yoga (as little as 20 min) R

Diet

Hormones

Supplements

Drugs

  • 2-deoxy-d-glucose R
  • NGF eye-drops R
  • Selegiline R

Other

  • Sauna (and heat shock) R
  • Semen (previously dubbed "ovulation-inducing factor") R

How to Decrease NGF

  • BCAAs (decreased in the hippocampus) R
  • Cortisol (in the cerebral cortex) R
  • Music (decreased it in hypothalamus) R
  • Ovary Removal R
  • Peroxynitrite R
  • Stress (in hippocampus and prefrontal cortex) R

Mechanism of Action

 
 

NGF is in a 7s, 130-kDa complex of 3 proteins when expressed: R

  1. Alpha-NGF
  2. Beta-NGF
  3. Gamma-NGF

NGF can bind to TRKA and P75. R

NGF binding to TRKA activates numerous signaling pathways, signaling neural cell survival and differentiation: R

  • Ras,
  • Rap-1
  • Cdc42-Rac-Rho family
  • PI-3-Kinase
  • PLCgamma

P75 promotes apoptosis in the absense of TRKa. R

  • Survival and PCD mechanisms are mediated through adaptor protein binding to the death domain of the p75NTR cytoplasmic tail. R
  • Survival occurs when recruited cytoplasmic adaptor proteins facilitate signal transduction through tumor necrosis factor receptor members such as TRAF6, which results in the release of nuclear factor κB (NF-κB) transcription activator. R
  • NF-κB regulates nuclear gene transcription to promote cell survival. R
  • Programmed cell death occurs when TRAF6 and neurotrophin receptor interacting factor (NRIF) are both recruited to activate c-Jun N-terminal kinase (JNK); which phosphorylates c-Jun. R
  • The activated transcription factor c-Jun regulates nuclear transcription to increase pro-apoptotic gene transcription. R

Genetics

 
 

NGF can drive the expression of genes such as bcl-2 by binding to the TrkA receptor, which stimulates the proliferation and survival of the target neuron. R

  • RS6330
    • A allele associated with low vagal activity (sex specific). R
    • In females GG hand higher levels of anxiety.  R
    • In males, GG had lower levels of anxiety. R
    • In men, GG had higher HRV. R
    • In women, GG had lower HRV. R
  • RS2072446
    • T associated with schizophrenia. R
    • C associated with Alzheimer's. R
  • RS4332358
    • Associated with depression and bipolar in women. R
  • RS734194
    • G allele may be protective against developing schizophrenia. R

More Research

  • Interactive Nerve growth factor pathway R
  • Superior cervical ganglia neurons that express p75NTR and TrkA die when treated with proNGF. R
  • Finger millet feeding on skin antioxidant status, nerve growth factor (NGF) production and wound healing parameters in healing the impaired early diabetic rats. R
  • All About Nerve Growth Factor and 50 Ways to Increase It R