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The Vagus Nerve, Neurotransmitters & Hormones

Written by Puya Yazdi, MD | Last updated:
Medically reviewed by
Genius Labs Science Team | Written by Puya Yazdi, MD | Last updated:

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Note that each number in parentheses [1, 2, 3, etc.] is a clickable link to peer-reviewed scientific studies. A plus sign next to the number “[1+, 2+, etc...]” means that the information is found within the full scientific study rather than the abstract.

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

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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