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Vasoactive Intestinal Peptide (VIP): Anti-Inflammatory

Written by Joe Cohen, BS | Last updated:

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If you’re having chronic inflammation or autoimmune issues, you need to learn about VIP and see the role it plays in your issues. This is a good hormone to read about because you can check it in your blood and also increase it with natural means (and a VIP spray if not).

I have solved my autoimmunity and chronic inflammation issues that held me down for most of my life, all across my site you can find the research I have compiled that has helped me become the best version of myself.


What is VIP?

Vasoactive intestinal peptide or VIP is a hormone produced in many tissues including the gut, pancreas, and suprachiasmatic nuclei (SCN) of the hypothalamus [1].

VIP stimulates the heart to contract, causes vasodilation and lowers blood pressure, increases glycogen breakdown and relaxes the smooth muscle of trachea, stomach and gall bladder [1].

VIP increases motility, induces muscle relaxation of the GI tract (lower esophageal sphincter, stomach, gallbladder), stimulates secretion of water into pancreatic juice (such as bicarbonate) and bile, stimulates pepsinogen, and causes inhibition of stomach acid secretion (by gastrin) and inhibits absorption of water from the intestines [1].

VIP, Hormones, And Neurotransmitters

VIP is highest in the morning and this helps it elevate cortisol to wake us up. This is also why cortisol levels are highest when we start our days and lowest in the night when we sleep [2].

VIP likely increases norepinephrine (by stimulating tyrosine hydroxylase, the rate-limiting enzyme that produces norepinephrine) [3].

VIP stimulates Growth Hormone secretion [1].

VIP stimulates prolactin release in turkeys [1].

VIP: The Good


VIP decreases most inflammatory cytokines.

VIP suppresses Th1 immune responses and promotes Th2-type responses [4, 5].

VIP decreases TGF-b1 in macrophages [6].

It suppresses inflammatory cytokines such as TNF, IL-2, IL-4, IL-5, IL-6, IL-12, IL-17 and chemokines [7].

VIP is needed for immune tolerance. It increases the anti-inflammatory IL-10 and promotes immune tolerant T regulatory (Treg) cells [7].

VIP inhibits TLR4 and MyD88 activation [8, 9].

In some instances, VIP can boost the immune system. In inflammatory sites, VIP may cooperate with proinflammatory mediators, such as TNF, to induce Dendritic Cell maturation [10]. VIP increased CCL5, which helps recruit T cells [11].

See this great picture that summarizes the immune effects of VIP and MSH.

Protects Against Autoimmune Disease

VIP may help autoimmune/inflammatory diseases, including rheumatoid arthritis, ulcerative colitis, multiple sclerosis, Parkinson’s disease, Crohn’s disease, septic shock, uveoretinitis, and experimental models of brain inflammation [5].

VIP has neuroprotective properties. It raises cellular resistance against oxidative stress and helps neuronal survival [12].

In patients with asthma, there is a loss of VIP from the lung nerve fibers, which results in a closing of the airways (lessens bronchodilation) [13].

VIP has shown potent anti-inflammatory effects in mouse models of arthritis [14].

Patients with early arthritis who are unable to increase VIP do worse, despite receiving more intense treatment [15].


VIP has antimicrobial, antibacterial and antifungal properties [16].

VIP displayed antimicrobial activity against Streptococcus mutans, Lactobacillus acidophilus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans [17].


VIP injected in the hippocampus exerted an anti-anxiety effect in rats [18].


Mice without VIP have elevated blood glucose, insulin, and leptin levels. They have enhanced taste preference to sweet foods (which is caused by leptin resistance in the tongue) [19].

Increases Fertility

VIP (from the SCN) increases the release of Gonadotropin Releasing Hormone (GnRH) [20], which is at least part of the reason why it’s important for fertility.

Female mice deficient in VIP produce about half the offspring of their normal sister mice even when mated to the same males [21].

VIP-deficient females have a disrupted estrous cycle [21].

It’s theorized that this is the mechanism by which disruption of the circadian system reduces female reproductive success [21].

Increases Sexual Function

VIP helps induce penile erections [22].

VIP increases vaginal lubrication in normal women, doubling the total volume of lubrication produced [1].

Improves Circadian Rhythms

VIP is also involved in synchronizing the timing of SCN function with the environmental light-dark cycle [1].

VIP-deficient mice have less strong (i.e lower amplitude) circadian rhythms as well as our of sync clocks with the SCN and other tissue [21].

In the adrenals, circadian rhythms (Per1) were lost in VIP-deficient mice, while in the liver, the most dramatic impact was on the phase or timing of the rhythm [21].

VIP: The Bad

Most of my clients are thin and suffering from autoimmunity or its precursors.

In the research, there is a trade-off between autoimmunity and cancer.

You know: those people who don’t seem to have any chronic inflammatory issues while constantly eating unhealthy food until they’re 50 – except being overweight, of course – until one day they suddenly get cancer.

VIP is an important candidate for being the main biological difference between such people.

May Contribute to Migraines, Eczema

Blood levels of VIP are elevated in patients with Eczema, which may indicate that it can cause the disease [23].

VIP is increased in women with chronic migraines [24].

May Contribute to Obesity

While VIP has some mixed effects, but on the whole, it’s thought to contribute to obesity.

VIP may explain in part why people who gain weight more easily often have lower chronic inflammation.

Anti-obesity effect:

  • VIP inhibits appetite (via a-MSH or CRH pathways) [25].

Pro-obesity effects:

  • VIP decreases basal metabolic rates [25].
  • VIP stimulates insulin secretion [26].
  • VIP decreases physical activity [25].

Can Contribute to Cancer

VIP combats inflammation and autoimmunity and can cause weight gain, but it also increases cancer risk.

VIP functions as a growth factor, and it has proangiogenic functions in breast and prostate cancer [27].

VIP increases VEGF and induces other biological mechanisms that induce tumor growth (EGFR and HER2 activation) and increase the production of cancer genes (c-fos, c-jun, and c-myc) oncogenes. There also is mounting evidence that VIP is involved in the pathogenesis of prostate cancer [27].

VIP stimulates prostate-specific antigen (PSA) secretion in prostate cancer [27].

How to Increase VIP

Besides glycine and prolonged fasts, there is insufficient information as to if and how much these methods can increase blood VIP.

If these natural methods don’t work enough, you can also try to get a script from your doc for an intranasal VIP.

1) Glycine

Glycine increased VIP by 3.2X in the daytime, which modulates the circadian rhythm [28].

Bone broth has glycine, but I prefer the supplemental form. Bone broth and chicken soup make me sleepy.

2) Nicotine

Nicotine increases VIP in the gut and brain tissue [29, 30, 31].

Nicotine does indeed increase gut flow pretty powerfully.

3) Vagus Nerve Stimulation

Stimulating the vagus nerve causes it to release VIP [32].

See my post on how to stimulate your vagus nerve.

4) Fasting

In a study of 6 young men, fasting for 59 hours increased VIP from 3.6 to 10.2 pmol.1(-1) [33].

5) L-Arginine

Long-term L-Arginine supplementation increases VIP in the rat small intestine [34].

6) Lemon and Limonene

Lemon and limonene increase VIP in gut tissue [35].


  • Circadian rhythm entrainment?
  • Leptin [36] – Leptin acts synergistically with TGF-beta to increase VIP.
  • TGF beta1 [36]
  • 5-HT3R [31] – activates VIP neurons
  • Secretin [37]
  • cAMP/CREB [38]
  • Baicalein [39] – increases VIP in certain cells infected by human cytomegalovirus [39]. Whether it increases VIP in people is unknown.
  • Ginger? Some people use ginger, but I haven’t seen any studies on ginger and VIP.

Exercise and VIP

VIP is elevated in the blood after aerobic exercise [27]. However, anti-VIP antibodies are also increased, which results in suppression of VIP – and on the whole, it seems like exercise decreases VIP over the long term [27].

Checking VIP

VIP is often low in mold illness/CIRS, which can contribute to a chronic inflammatory state.

I would recommend checking your VIP if you have chronic inflammatory or autoimmune issues. This article will explain the importance of VIP and natural ways to increase it.

In healthy controls, a median VIP-serum level of 42.44 +/- 2.540 pg/ml (range, 12.9-98.5 pg/ml) was found [40]. In healthy women, VIP averaged 88.5 pg/ml… Normal range: 23 – 63 [41].

Want More Targeted Ways to Combat Inflammation?

If you’re interested in natural and more targeted ways of lowering your inflammation, we at SelfHacked recommend checking out this inflammation wellness report. It gives genetic-based diet, lifestyle and supplement tips that can help reduce inflammation levels. The recommendations are personalized based on your genes.

SelfDecode is a sister company of SelfHacked. The proceeds from your purchase of this product are reinvested into our research and development, in order to serve you better. Thank you for your support.

About the Author

Joe Cohen, BS

Joe Cohen won the genetic lottery of bad genes. As a kid, he suffered from inflammation, brain fog, fatigue, digestive problems, anxiety, depression, and other issues that were poorly understood in both conventional and alternative medicine.Frustrated by the lack of good information and tools, Joe decided to embark on a journey of self-experimentation and self-learning to improve his health--something that has since become known as “biohacking”. With thousands of experiments and pubmed articles under his belt, Joe founded SelfHacked, the resource that was missing when he needed it. SelfHacked now gets millions of monthly readers.Joe is a thriving entrepreneur, author and speaker. He is the CEO of SelfHacked, SelfDecode and LabTestAnalyzer.His mission is to help people gain access to the most up-to-date, unbiased, and science-based ways to optimize their health.
Joe has been studying health sciences for 17 years and has read over 30,000 PubMed articles. He's given consultations to over 1000 people who have sought his health advice. After completing the pre-med requirements at university, he founded SelfHacked because he wanted to make a big impact in improving global health. He's written hundreds of science posts, multiple books on improving health, and speaks at various health conferences. He's keen on building a brain-trust of top scientists who will improve the level of accuracy of health content on the web. He's also founded SelfDecode and LabTestAnalyzer, popular genetic and lab software tools to improve health.

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