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Written by Dr. Welsh, Article reviewed and edited by Dr. Fine M.D..
Published on 19 August 2014

Ghrelin Hormone Guide

What is Ghrelin?

Ghrelin is the primary hormone in the human body which regulates the sensation of hunger. It is considered a partner to a hormone known as Leptin, which controls satiation. Whereas Leptin is produced primarily by adipose fat tissue, Ghrelin is released by special cells throughout the digestive system. After Ghrelin is released, the hormone circulates through the body and activates at sites throughout the nervous system, in particular, the hypothalamus.

Like Leptin, in addition to impacting hunger signals, Ghrelin also has a role in metabolism and the usage and storage of energy.

When is Ghrelin Released?

Ghrelin is produced by the stomach when the stomach is empty, and the release of the hormone is suppressed when the stomach is stretched. The primary influence of Ghrelin is upon the hypothalamus, where it triggers the sensation of hunger and encourages the stomach to release acid in preparation of its next meal. It also readies the entire digestive system to process and move food through the system.

Leptin and Ghrelin both trigger activity upon the same receptors in the hypothalamus, although Ghrelin encourages hunger and Leptin suppresses it.

Ghrelin also alters the sensitivity of a certain pleasure center of the brain known as the ventral tegmental area, an area which plays a major role in both addiction and sexual libido. In particular, Ghrelin has a powerful influence on both acetylcholine and dopamine production.

Ghrelin is just one of many hormones that help human beings (and other animals) establish a routine pattern of energy distribution. It encourages the body to intake calories which will be converted into energy by stimulating hunger, and also alters the way that the body uses energy, in terms of immediate heat generation, adipose fat storage, and the process of the ATP cycle.

Ghrelin and Leptin Ideally Create Metabolic Homeostasis

When Ghrelin and Leptin are interacting as they should, it helps to promote an ideal physiological state, but when these hormones get out of their natural rhythms, it can lead to increased body weight and reduced metabolism, as well as powerful sensations of hunger which encourage eating junk food and other foods dense in calories.

Leptin controls the way that the body responds to food via signals from body fat, while Ghrelin controls the way that the body responds to food from the stomach itself. There are a number of pathways through which Ghrelin achieves this, some of which are not fully understood at this time. There are also synthetic molecules which imitate the function of Ghrelin which have the ability to both promote weight gain and increase appetite by activating receptor sites on the arcuate nucleus.

Insulin, Leptin, and Ghrelin

The ability of Ghrelin receptors to accept stimulation is affected both by the influence of insulin and Leptin. Also, Ghrelin encourages eating full meals because it suppresses the body's ability to feel the stomach stretch until toward the end of the meal when Ghrelin levels decline.

In addition to directly controlling hunger, Ghrelin also promotes the release of pleasure hormones which encourage an individual to regularly eat, but can also promote overeating as well as addiction if a patient lacks willpower and self-control. In fact, alcohol dependency requires Ghrelin to activate receptors on the hypothalamus, and this is also one of the influences which encourage people to prefer certain foods over others.

Ghrelin and Eating Habits

Ghrelin is a powerful hormonal force which controls both feeding and appetite in animals, including humans. Ghrelin levels drop after we eat a meal, and slowly rise over time, increasing our hunger and desire to eat. Ghrelin peaks immediately before eating and drops to its lowest levels after the meal has concluded.

Ghrelin Injections, and the injection of Synthetic Ghrelin Analogues, have the ability to increase hunger and appetite dependent upon the dose of the hormone that is administered. This means that the more Ghrelin that is administered, the more calories that a patient will consume over time. This does not make individuals eat more at every meal, however. It makes them become hungry again much more quickly than they normally would, so they eat more meals each day.

In animal species, the administration of Ghrelin causes the animal to search for food more aggressively, and increases the prevalence of any activities related to meal habits, including hoarding, foraging, or sniffing out food.

Ghrelin and Metabolism

Body mass is controlled through metabolism. At its simplest, this simply means that weight is controlled by adjusting how calories are taken in and how calories are burned from day to day. The more Ghrelin that an animal produces, the more they will weigh, as a general rule. Based on this information, it is believed that Ghrelin acts as an intermediary between adipose fat deposits and the brain.

Ghrelin is dependent upon the weight of the individual. The less than a person weights, the more Ghrelin that their body will produce, while on the other hand, the more that a person weighs, the less Ghrelin that they will produce. This may be one reason why many people that are overweight don't eat as often as their peers, but eat larger meals as a result of their lack of self control.

Under normal circumstances, Ghrelin works in the body as a means to keep weight at an average healthy level, mediating the body's use of energy and its mass.

Ghrelin and the Digestive System

Ghrelin acts as an anti-inflammatory in the digestive system and prevents cells from spontaneously dying during times of internal stress and inflammation. Ghrelin generally promotes the activity of other anti-inflammatory hormones and compounds while limiting the activity of those that cause inflammation. For this reason, researchers hypothesize that medically administered Ghrelin may one day be useful in promoting gastrointestinal health during these times of stress. Ghrelin also appears to help the interior of the digestive system rehabilitate itself after damage and injury.

In the case of pancreatic and gastrointestinal cancers, elevated Ghrelin levels can exacerbate the illness.

Ghrelin and the Pancreas

Ghrelin and insulin are related hormones, and the presence of one impacts the activity of the other. There are Ghrelin receptors on the pancreas, and when Ghrelin activates these points, it slows down the release of insulin in response to the presence of glucose. This means that Ghrelin slows down the rate at which the body processes sugar as it circulates through the body.

Ghrelin and Heart Health

Ghrelin is beneficial to heart health because it inhibits the formation of fatty deposits in the arteries, and it also encourages the healthy function of the endothelium, the inner lining of the blood vessels.

Ghrelin, Memory, and Learning

The hippocampus is the center for learning in the brain. Ghrelin plays a role in all of this, and also encourages the production of Human Growth Hormone. Ghrelin circulates through the blood stream and passes through the blood-brain barrier at the hippocampus, and encourages the development of new connections in the brain

There is some evidence that the brain is able to retain information at the highest levels when Ghrelin levels are higher, which means that when people are full, they may have slightly more trouble learning than when they are hungry. From an evolutionary perspective, it does seem beneficial to have additional horsepower in the brain when the body requires food, and for the mind to slow down after a meal has been found and consumed. This process is apparent in animal studies, and it is hypothesized that in humans this same mechanism is at play, at least to a certain extent.

Ghrelin and Depression

Animal research has shown that Ghrelin promotes a healthier psychological profile and inhibits depression. Lab mice which don't produce Ghrelin experience greater levels of anxiety when they are exposed to both physical and psychological stress. Under normal circumstances, Ghrelin has the ability to interact with the hypothalamic-pituitary-adrenal axis in a way that reduces the effects of stress.

Also, animal studies have shown that Ghrelin acts like an anti-depressant in laboratory mice, as rodents with elevated levels of the hormone showed fewer signs of stress than their peers without Ghrelin. Furthermore, rodents that were unable to produce Ghrelin were less likely to interact with other rats around them.

When these lab rodents were provided an anti-depressant, it counteracted the social inhibition experienced resulting from a lack of Ghrelin, which suggests that Ghrelin helps ward off depression by some underlying mechanism.

Ghrelin and Sleep

Elevated Ghrelin Levels are associated with shorter periods of rest, and this is also associated with being overweight. The more Ghrelin that is present in the blood stream, the less sleep that an individual will experience. Also, those that sleep well through the night are less likely to experience obesity, and their Ghrelin levels tend to be lower.

Ghrelin and Fear Response

Humans and animals have a tendency to experience latent fear as a result of past experiences of stress. Ghrelin plays a role in this, as the body releases Ghrelin in response to such fear, which makes the source of the fear easier to retain. Stress affects Ghrelin concentrations even when the body is not producing adrenal hormones such as cortisol. When Ghrelin stimulation is inhibited, this suppresses the brain's tendency to learn what to fear more effectively under stress, although it does not affect adrenal response to stress.

In the future, there will likely be medications that use synthetic Ghrelin or Ghrelin analogues as a means to limit the effects of mental disorders caused by stress.

Ghrelin and Dopamine

Dopamine is the primary pleasure hormone that is produced by the body. Ghrelin increases the level of dopamine that is present in the substantia nigra, which is the reward center of the brain. Upon eating or engaging in any other pleasurable activity, this enhances the sensation of pleasure.

Ghrelin and Reproductive Health

Ghrelin inhibits the release of precursor hormones which produce sex hormones and sperm, whereas Leptin encourages the production of these hormones. It is unclear to what extent that this may limit fertility. From an evolutionary standpoint, it makes sense that during times of hunger, reproduction would be a secondary concern, whereas during periods of satiation and abundance, sex drive and function would increase.

Prenatal Health and Ghrelin Production

During the fetal stage, the developing lungs produce Ghrelin in order to accelerate the growth of the organ. Also, there is a connection between the concentration of Ghrelin in the umbilical cord and the weight of the child at birth.

Ghrelin, Obesity, and Anorexia

As we mentioned earlier, individuals that are overweight or obese do not produce as much Ghrelin as their thinner counterparts. For this reason, it does not seem that Ghrelin is a contributor to weight gain, although its high or low levels can affect other aspects of physiological health. The exception to this is patients that suffer from Prader-Willi syndrome. Among these patients, Ghrelin levels do promote obesity.

Individuals that suffer from anorexia have exceptionally high blood-concentrations of Ghrelin. The issue is that their bodies override these normal physiological cues to eat. Clinical research has shown that by introducing exogenous Ghrelin intravenously, it is possible to increase calorie intake among patients with anorexia by as much as 36%.

Under normal, healthy circumstances, Ghrelin levels are low around bedtime and increase slowly through the course of the night. Overweight and obese individuals are more likely to experience elevated Ghrelin levels at inappropriate times, which is evidence toward the hypothesis that obesity is a condition that is exacerbated by an incorrect circadian rhythm.

Being in front of a computer screen or other source of abundant light during the late evening can interrupt the natural rise and fall or Ghrelin levels at night. Also, individuals that don't get enough sleep at night produce more Ghrelin, because sleep naturally has a depressant effect upon the hormone. Poor sleeping habits promote the suppression of leptin and the release of Ghrelin, which promotes overeating.

Potential Medical Uses of Ghrelin in the Future

  • Ghrelin may also prove to be an effective means to promote the normal muscle activity of the stomach in individuals suffering from gastroparesis.

  • In animal research, Ghrelin has proven effective at reducing the number and severity of seizures that afflicted animals experience. This may cross over into humans.

  • Ghrelin will soon be used as a treatment for many forms of wasting disease, and may assist patients being treated for kidney failure.

Ghrelin and Appetite: A Research Study

New research shows that elevated levels of Ghrelin promote poor dietary choices, which is why many people may be more prone to eating unhealthy foods packed with calories like cookies and cake.

Simply having elevated Ghrelin in circulation is as powerful of an influence on diet as the act of fasting, both of which encourage desire for calorie-dense foods. Ghrelin reaches very high levels during the act of fasting, but the administration of synthetic Ghrelin can mimic the physiological and psychological desires associated with such a fast, even if the patient does not engage in the activity.

This is because of the way that Ghrelin interacts with the reward centers of the brain. In this study, it was found that synthetic Ghrelin significantly increased the activity in the area of the brain which activates in response to pleasure.

The main researcher in this study, Dr. Goldstone, was interested in seeing how the administration of Ghrelin via injection compared to the act of fasting in relationship to dietary choice.

His study involved eighteen patients, all around the age of 23, all of which were of average weight. They were required to fast the night before and come in without breakfast, and they visited the medical location on three occasions, all of which were at least seven days between.

Each visit, patients either stayed on the fast or ate a meal of 730 calories. After they were fed or required to remain on their fast, they were administered with an injection of either Ghrelin or saline. In order to ensure that the patients' bodies reacted to the Ghrelin injection, they were tested for elevated HGH levels, which rise at the same time that Ghrelin Levels rise in the blood stream.

Ghrelin Research Procedures

Rather than eating after the injection, the subjects were shown various images of foods, sixty of which were low calorie foods, and sixty of which were foods with high calories. Interspersed among these pictures were photos of things seen around the house, to act as a control. During this rating process, their brains were scanned in an MRI machine, meaning that the patient could both provide a qualitative response while the researchers also measured the neurological response to the food stimulus.

How Does Ghrelin Affect Desire for Food?

What researchers discovered was that Ghrelin had no effect on the participants' interest in foods with low calories, while it did increase the desire for foods with a lot of calories. In particular, Ghrelin increased the desire for sweets the most.

One particular area of the brain that was closely monitored during these tests was the anterior orbital frontal cortex, which is the location of the brain that stores the desire that the brain has for particular foods. He found that satiated individuals that received saline did not experience high levels of activation in this area, whereas those that received Ghrelin still experienced activity in this area even when the patient was fed prior to the imaging session.

Does Ghrelin Contribute to Obesity?

Ghrelin may not directly cause obesity, but it does prevent the body from changing its pattern of nutrition intake. Ghrelin levels remain low as long as the obese patient stays at his or her stable weight, but as soon as he or she tries to lose the weight, Ghrelin levels increase dramatically. It is believed that one day, there will be treatments available which block the body's production of Ghrelin during dieting in order to promote weight loss and treat obesity.


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