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The Vagus Nerve, Neurotransmitters & Hormones

Written by Joe Cohen, BS | Last updated:
Medically reviewed by
SelfDecode Science Team | Written by Joe Cohen, BS | Last updated:

This post focuses on the science behind various neurotransmitters and hormones and their link to vagus nerve activity. 

Most of the research has been conducted in animals or cells. We still know little about the interplay between the vagus nerve, hormones, and neurotransmitters in humans. 

Our aim is to discuss research findings. We strictly advise against taking any hormones to affect vagus nerve activity. 

Serotonin

Serotonin seems to be capable of activating the vagus nerve through various receptors: 5HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 [1, 2, 3, 4].

On the other hand, 5-HT7 receptors may reduce vagus activation [5, 6].

Thus, serotonin has some mixed effects. 5-HTP is a supplement that may increase serotonin, but it’s unknown whether it affects the vagus nerve. 

Oxytocin

Oxytocin may increase vagal nerve activity from the brain to the gut (in the brain and orally ingested), which induces relaxation and decreases appetite [7].

Mice who had their vagus taken out didn’t exhibit the appetite-reducing effects of oxytocin [7].

Thyroid Hormones

In rats, thyroid hormones (T3) increased appetite through activating the vagus nerve [8].

Orexin

Orexin neurons are found in centers which control vagus nerve activation from the brain [9].

Orexin stimulates the vagus nerve from the brain, which promotes gut flow. It can stimulate the pancreas, too, according to an animal study [10].

Orexin is implicated in increasing glucose tolerance or insulin sensitivity via the liver vagus nerve [11].

On the other hand, orexin might inhibit the activation of the vagus nerve signals to the brain by competing with CCK [12].

Orexin might stimulate the vagus nerve in the brain, liver, and pancreas, but human data are needed.

Ghrelin

Ghrelin is hypothesized to increase growth hormone and hunger by stimulating the vagus nerve signal from the brain to the gut, and this is abolished by capsaicin (in chili) in animals [13].

Ghrelin may stimulate the pancreas from the brain via the vagus [14].

Leptin

Vagal impulses to the brain appear to be also activated by leptin. Leptin potentiates the CCK-induced activation of the vagus nerve [15].

Leptin-resistant animals were hungrier since the vagus nerve became less sensitive to CCK [16].

However, another study found that leptin effect on the vagus signal doesn’t play a major role in food intake [17].

More research is needed to clarify these findings. 

Leptin might cause satiety by activating the vagus nerve, but its effects seems to be mixed. Further studies are required.

CRH

CRH has variable effects on the vagus nerve. Scientists think it decreases its activity from the brain to the heart. Vagus nerve activation will slow the heart rate, but CRH seems to inhibit this and increases heart rate–at least in animals [18].

Researchers are investigating whether CRH stimulates the vagus impulse from the brain to the colon (by activating the dorsal nucleus of vagi, via cholinergic transmission) [19].

Other

Vagus nerve stimulation seems to normalize an overactive nervous system (HPA axis), according to some experimental hypotheses [20].

Some scientists believe that the vagus nerve may help reduce pain, and this is the proposed mechanism by which estradiol reduces pain in certain circumstances. However, these pathways have not been properly verified in humans [21].

Besides influencing the release of oxytocin, the vagus nerve is thought to be important for releasing testosterone. Research teams are investigating whether vagus nerve imbalances are connected to low testosterone in some men [22].

One intriguing study hypothesized that although testosterone can make people more aggressive, this is not the case when the vagus nerve is functioning right. These findings have yet to be replicated [23].

Proper functioning of the vagus nerve is important for the production of GHRH (growth hormone-releasing hormone) and IGF-1 in animals [24].

The vagus nerve may stimulate other hormones such as parathyroid hormone, which is important for the conversion of vitamin D3 to active vitamin D (1,25). A direct influence of the vagus nerve on vitamin D status hasn’t been established, though [25].

Stimulation of the vagus nerve may also produce the release of vasoactive intestinal peptide (VIP [26].

NPY might block some of the vagus nerve effects, according to animal data. NPY is described as an anti-anxiety and hunger-increasing hormone, which prevents heart rate decrease from vagal stimulation. How it impacts vagus nerve stimulation in humans is unknown [27].

The vagus nerve affects many hormones, some of which are implicated in lowering pain and anxiety. These pathways are still being explored in humans.

About the Author

Joe Cohen, BS

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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