Nerve Growth Factor plays an important role in cognitive function, depression, inflammation & more. Learn the positive effects of NGF & how to increase it.

What is Nerve Growth Factor?

Nerve growth factor (NGF) is one of a group of small protein-like molecules called neurotrophins (BDNF is another) that are responsible for the development of new neurons, and for the health and maintenance of mature ones.

NGF promotes growth, maintenance, and survival of neurons and axons. It also helps repair myelin sheath, the coating around the axons [1].

Animal testing has shown that as the production of NGF decreases in the brain, one’s ability to form new connections and to retain and access memories is impaired. NGF can save degenerating nerves and restore function [2].

Dr. Rita Levi-Montalcini won a Nobel Prize for discovering nerve growth factor in 1986 and she used NGF eye drops to increase her life- and health-span [3].

In a study of 157 normal people, NGF was on average 194 pg/ml. Age didn’t make a significant difference amongst the participants, but NGF was significantly lower in females (112 pg/ml) than in males (243 pg/ml) [4].

Low Versus High NGF

Low NGF levels are found in a variety of common Western diseases, including atherosclerosis, obesity, type 2 diabetes and metabolic syndrome [5].

High NGF levels are found in a number of autoimmune diseases, accompanied by increased numbers of mast cells, which produce histamine and which are also able to produce NGF [6].

Positive Effects

1) May Help Depression

Blood levels of NGF were significantly lower in those with Major Depressive Disorder compared to controls [7].

Exercise increased NGF (and BDNF & synapsin I), which improved the survival of neurons in the hippocampus and simultaneously improved depression by increasing the serotonin-producing cells in the brain stem [8].

Chrysin is a flavonoid found in honey and some plants. The chrysin-induced increase of NGF is possibly behind its antidepressant effect (20mg/kg) in mice [9].

2) May Help Multiple Sclerosis

In an animal model of human brain demyelinating diseases (e.g. Multiple Sclerosis), NGF delayed onset, lowered inflammation, and lessened tissue injury [10].

NGF promotes growth and repair of myelin damage [11].

NGF also directly controls some of the main structural proteins of the myelin sheath [11].

NGF induces the production of BDNF, which is also important for the myelination of nerves [11].

Because of NGF’s abilities to protect the brain and balance the immune system, it is being studied for a number of brain disorders, including Multiple Sclerosis, Alzheimer’s disease, and Parkinson’s disease [12].

3) May Help Alzheimer’s Disease

Substances that raise acetylcholine have shown benefit for Alzheimer‘s disease. Recent animal studies show that NGF selectively protects acetylcholine activated neurons, showing positive implications for the treatment of Alzheimer’s [13].

In a study of 10 Alzheimer’s patients and NGF gene transfer therapy, degenerating neurons sprouted from their axons, there was tissue growth, and there was an improvement of function [14].

The ability of the brain to convert proNGF to mature NGF is faulty in both Alzheimers disease and in Down Syndrome, resulting in neurons that are dysfunctional. Amyloid-β plaque formation and brain inflammation may be causes [15].

4) Schizophrenia

Studies have found that certain genetic variations in the NGF and NGF receptor are associated with decreased blood levels of these proteins and increase the risk for schizophrenia [16].

5) Cardiovascular

In a mouse model of injury to the artery, NGF regenerated the nerve around the blood vessels and subsequently helped form new blood vessels, supporting their development and stabilization [17].

NGF helps repair the heart after a heart attack [18].

6) Diabetes

NGF seems to be important for pancreatic health. If NGF is taken away, the pancreatic beta cells die [19].

Low blood levels of NGF are associated with diabetic neuropathy [20].

7) Supports Fertility

NGF is very much involved in the reproductive system. It’s so important that it’s also been referred to as Ovulation-inducing factor (OIF) [21].

Recent studies have confirmed that it induces ovulation (the release of the egg from ovaries) in some mammals, which can help with fertility [21].

Low levels of NGF (and BDNF) in the follicular fluid of the ovary may lessen the ovary’s ability to provide egg cells and may also be associated with a higher risk of endometriosis [22].

It is abundant in semen.

Negative Effects

While NGF does a lot of good things, it may be problematic in some ways. The issue with some of these studies is that in certain states of disease, NGF can increase, which doesn’t mean that NGF causes the disease. Rather, it may just be a correlation. But overall, it seems like NGF can contribute to certain issues.

1) Inflammation, Pain, and Injury

It’s assumed that NGF can contribute to pain.

In an experiment using human lung cells, high levels of NGF were associated with chronic inflammation [23].

NGF is often high in patients with chronic pain (interstitial cystitis/painful bladder syndrome, chronic prostatitis/chronic pelvic pain syndrome, osteoarthritis, diabetic peripheral neuropathy, and psoriasis) but not in all cases [24].

Increased NGF might be part of the inflammatory response to brain injury [25, 26].

NGF activates mast cells, which causes the release of histamine. BDNF and other neurotrophins, however, do not activate mast cells [27].

NGF may play a role in regulating the interactions of the nervous system, hormonal system, and immune system, keeping it in balance. A number of autoimmune conditions have high NGF as well as more mast cells [6].

NGF is one mechanism by which stress increases inflammation and autoimmunity (neuroimmune interactions) [6].

A drug that inhibits NGF is used for arthritic pain [28].

2) Cancer

According to research, NGF (as well as BDNF) stimulates the spread and survival of tumor cells and promotes new blood vessel production in tumors [29].

However, NGF prevents the spread of cancer cells in hypothalamic or pituitary tumors and small cell lung cancer (SCLC). Simultaneous treatment with Vitamin A (retinoic acid) enhances the effect [30].

How to Increase Nerve Growth Factor (NGF)

Lifestyle

  1. Social Enrichment early in life – Mice reared in a more social environment had higher NGF in selected brain areas (hippocampus and hypothalamus) as adults [31].
  2. Yoga (even a single 20-minute session) [32, 1]
  3. Stress reduction  Chronic mild stress decreased the concentration of NGF in the rat hypothalamus [33, 9].
  4. Exercise: Low-Intensity Resistance Training [34], Treadmill exercise [358].
  5. Falling in love [36]
  6. Semen and Injaculation (for men)
  7. Intense Exercise: Allergic and neuro-immune disorders such as ALS tend to occur more frequently among athletes. NGF increases with stressors and allergies in humans and after physical exercise in animals. A study of blood levels of NGF in Olympic athletes showed significantly higher levels of NGF than controls [37].

Hormones That Increase NGF

  1. Estrogen
  2. Progesterone

Removal of ovaries (which produce Estrogen & Progesterone) caused a significant decrease of NGF in the uterus [38].

When mice with their ovaries removed were treated with estrogen and/or progesterone, NGF protein levels restored to normal [38].

Removing the ovaries did not affect the NGF levels in the salivary glands or the heart [38].

Fluctuations in the expression of NGF, in conjunction with other factors, may help to explain gender differences in pain sensation and inflammation [38].

Supplements to Increase NGF

  1. Nicotine – Activates NGF in cultured spinal cord neurons [39].
  2. Butyrate [40]
  3. PQQ – An antioxidant that also stimulates NGF. It strongly promotes peripheral nerve regeneration [41].
  4. ALCAR – Increases levels of neurotrophins such as NGF [42, 43] and improves nerve regeneration in rats.
  5. Rosemary (Carnosic acid) – Induces NGF production [44].
  6. Quercetin – Promotes nerve growth, and has shown the ability to regenerate peripheral nerves [4546].
  7. Ginkgo Biloba (Has Quercetin) [47]
  8. Lion’s Mane (Hericium erinaceus) – An edible mushroom that has been shown to boost NGF [48].
  9. Zinc  Zinc may increase NGF; however, memory was improved only when Vitamin A was sufficient [49]. Zinc may also bind to NGF, blocking its effect, but that was lessened under a more acidic pH [50].
  10. Lithium – A 14-day Lithium trial increased NGF in specific parts of the brain: frontal cortex, amygdala, hippocampus, and limbic forebrain in adult rats [51].
  11. Vitamin D3 – Treatment with the active form of vitamin D for 24 hours increased the NGF concentration in the brain 2- to 3-fold. Pretreatment with Forskolin doubled the results so that NGF was multiplied by 6 [52]. However, this effect could be impaired if your blood sugar is high [53].
  12. Melatonin – A 30-day injection of 1 mcg increased NGF in the submandibular gland of mice. These effects were not observed when the dose of melatonin was increased to 10 and 50 μg daily [54].
  13. DHEA – Might induce overproduction of NGF cortical neurons [55].
  14. Astragalus – The extract may act as a nerve-growth promoting factor [56].
  15. Huperzine A – An alkaloid from herbs that seems to boost NGF [57].
  16. Bupleurum (Chinese herb Radix Bupleuri) – Raises blood levels of NGF [58].
  17. Ashitaba – 10 ml (Two Teaspoons) Increases NGF production by 20%
  18. Yohimbine – Increased blood levels of norepinephrine, which upregulates the expression of NGF (in rats).
  19. Chrysin – A flavonoid found in honey and some plants, it increases NGF [9].
  20. Royal jelly Topically, royal jelly increases NGF [59, 60].
  21. Rehmannia – Improves learning and memory in rats, possibly due to increased NGF in the hippocampus [61].
  22. Polygala tenuifolia – The root extract (used in Chinese Medicine) increased NGF secretion in the lab [62].

Drugs to Increase NGF

  1. Idebenone [63, 64] – Stimulates NGF, antioxidant properties have been disputed [63].
  2. Selegiline (drug) – A metabolite of Selegiline, desmethylselegiline, elevates NGF, BDNF, and GDNF [65].
  3. Noopept – A “smart drug” that has been shown to stimulate the expression of NGF in rat hippocampus [66].
  4. 2-deoxy-D-glucose (2-DG) – A compound known to produce ketones. 2-DG significantly increased expression of NGF in mice [67].
  5. NGF eye drops (rather expensive, but apparently effective) [68].

Supplements That Support NGF Activity

  1. Sauna/Heat Shock – Enhances NGF-induced nerve growth [69].
  2. Green Tea/EGCG – Green tea polyphenols increase NGF-induced nerve growth. Among the polyphenols present in green tea, only EGCG significantly enhanced NGF-induced neuronal growth [70, 71].
  3. Milk Thistle – Enhanced NGF-induced nerve growth and prolonged their survival in the lab [72].
  4. DHA – Increases NGF-induced neuronal growth [73, 74].
  5. Vitamin A – Increases NGF receptors and sensitizes cells to the effects of NGF [75].
  6. Alcohol – Increases NGF-induced neuronal growth [73].
  7. Phosphatidylserine – Protects receptors. PS helps older rats retain more quality neurons and a higher density of NGF receptors [76].
  8. Gotu Kola (Centella asiatica) – Caused a marked increase in neurite outgrowth in the presence of NGF [77]. 
  9. Alpha-GPC (choline alfoscerate) – May increase the expression of NGF receptors in the brain [78].
  10. Acetyl-L-carnitine arginate is a patented form of carnitine that stimulates the outgrowth of neurons in the brain. Studies show that ALCA stimulates the growth of neurites by 19.5%, which is almost four times better than acetyl-L-carnitine.
  11. Uridine + Choline + DHA – Feeding omega-3s (DHA or EPA) to gerbils eating a choline-rich diet improved the nerve membranes, especially when also given with a dietary source of uridine [79]. This combination significantly improved performance, implying better brain function [8081].
    • Uridine converts to a form of choline called GDP-choline when it enters the brain [82].
    • Uridine Monophosphate is the compound used in brain research studies. It is a major component of RNA, which is rich in foods such as organ meats, brewer’s yeast, tomatoes, and broccoli. When these foods are digested, uridine is released from RNA and is absorbed in the gut.
  12. Forskolin – Further increases NGF [83].
  13. Genistein – Enhanced the NGF-induced nerve growth in rat cells [84].
  14. Nardosinone (from Chinese spikenard) Greatly enhances NGF-induced nerve growth [85, 86].
  15. 4-O-methylhonokiol – A compound from Magnolia officinalis, it promotes the release of NGF and increases nerve growth [87].

NGF SNPs

rs6330

This SNP changes an amino acid in the NGF gene and therefore affects its function (G=Ala, A=Val).

A-allele carriers are at increased susceptibility to anxiety by its association with low vagal activity [88].

  • In females, GG had higher levels of anxiety than AG or AA [89].
  • In males, GG had lower levels of anxiety than AG or AA [89].

Vagal activity impacts heart rate variability scores:

  • In men, GG had a higher heart rate variability (high-frequency power and RMSSD) [88].
  • In women, GG had a nonsignificantly lower heart rate variability [88].

Nerve growth factor (NGF) plays a role in the functioning of the basal forebrain cholinergic neurons, which are involved in attentional systems, and are impaired in Alzheimer’s Disease.

  • The G allele was significantly more common in people with ADHD (P=.05) [90].
  • The “A” allele was associated with a 1.47X increased risk of Alzheimer’s [91].

rs2072446

The T allele is associated with schizophrenia, which is associated with decreased blood levels of these Nerve Growth Factor [16].

Although C is the common allele, it increases the risk of Alzheimer’s in people with a family history [92].

rs4332358

This SNP is associated with affective disorders such as depression or bipolar in women (doesn’t specify allele) [93].

rs734194

G or the less common allele might be protective against developing schizophrenia [16].

Check out SelfDecode to see if you have these SNPs.

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