Known as the hunger hormone, ghrelin stimulates appetite and promotes eating. It isn’t necessarily “good” or “bad,” though it may become dysregulated in various health conditions and disease states. When is ghrelin beneficial, and when can it do harm? Learn more here.
The less body fat we carry, the more ghrelin we produce: a mechanism by which the body maintains body weight and promote increased food intake if it doesn’t have sufficient fat reserves .
Ghrelin gets released into the blood and goes into the brain, where it sends a hunger signal to the hypothalamus. Ghrelin receptors are found in high concentrations in the hypothalamus of the brain and in the pituitary gland [9, 10].
Ghrelin sends a signal that we don’t have enough energy, that we need to eat, and that we need to conserve our energy .
Chronically elevated levels of ghrelin are associated with obesity, overeating, and inflammation-related diseases including ulcerative colitis, Crohn’s disease, pancreatitis, and possibly rheumatoid arthritis .
Ghrelin affects the immune system, the reproductive system, strengthens the bones, and promotes muscle development .
This section is a discussion of the role of ghrelin in general health. None of these should be taken as a reason to try to increase ghrelin levels artificially; if the ghrelin system is dysregulated, an underlying health condition is likely at fault.
If you feel that you are unusually hungry, if you have runaway weight gain, or if you are suffering from another symptom that you believe could be connected to ghrelin, talk to your doctor about the possible causes and appropriate treatment or management plans available to you.
A number of reports describe ghrelin to be a potent anti-inflammatory mediator both in organisms and in cells and a promising therapeutic agent for the treatment of inflammatory diseases and injury.
Ghrelin reduces cell death and increases cell production .
Elderly patients aged 70 and older, who cannot produce as much ghrelin as younger patients, experience more severe inflammatory disease symptoms .
Ghrelin may help patients with autoimmune/inflammatory diseases, including rheumatoid arthritis, ulcerative colitis, multiple sclerosis, Parkinson’s disease, Crohn’s disease, cardiovascular disease, and inflammation from brain injury .
Ghrelin protects the lungs, liver, kidneys, and other organs from toxic by-products of oxygen reactions and inflammation injury .
Ghrelin has shown potent anti-inflammatory effects in rat and mice models of arthritis, resulting in a slowed progression of the disease .
Ghrelin also protects the heart from inflammation injury and improves heart function in mouse models of heart disease .
Ghrelin produced in the stomach can enter the hippocampus (an area of the brain important for long-term memory storage) through the blood.
Similarly, rats injected with ghrelin demonstrated better memory retention .
Restricting calorie intake, which has been shown to increase ghrelin levels, improved memory in elderly people .
Ghrelin may enhance neuronal firing by activating the NMDA receptor .
In cells, ghrelin dose-dependently enhances the contraction of stomach muscle cells when stimulated .
Ghrelin decreases blood pressure in healthy subjects .
In animal models with heart failure, ghrelin improved cardiac output .
In patients with chronic heart failure, ghrelin improved heart function, increased heart output and increased muscle strength .
The mechanisms responsible for the low blood pressure effects of ghrelin include the suppression of fight or flight activity , inhibiting the renin-angiotensin system in humans  or direct vasodilatory action [39, 40].
Acute ghrelin treatment improved survival in a heart attack by preventing an increase in the frequency of heart arrhythmias (rats) .
In humans, blood ghrelin level was positively correlated with bone mineral density in peri-, post-, and premenopausal women .
In a randomized, double-blind, placebo-controlled study, ghrelin infusion had no acute effect on markers of bone turnover in healthy controls. However, people who had high ghrelin levels had less bone destruction .
Ghrelin causes the release of growth hormone by activating the growth hormone secretagogue receptor .
The growth hormone secretagogue receptor (GHSR) increases growth hormone release .
Many of the benefits of ghrelin come as a result of activating this receptor.
Ghrelin increases the production of mitochondria .
Ghrelin is a robust activator of mitochondrial function in the hypothalamus .
This section is a discussion of the role of ghrelin in general health. None of these should be taken as a reason to try to decrease ghrelin levels artificially; if the ghrelin system is dysregulated, an underlying health condition is likely at fault.
If you feel that you are suffering from symptoms that you believe could be connected to ghrelin, talk to your doctor about the possible causes and appropriate treatment or management plans available to you.
Whether ghrelin acts as an antidepressant or as a depressant is debated.
Recent studies suggest that Ghrelin may have antidepressant properties.
Antidepressant-like behaviors in mice have been observed in response to increased ghrelin levels. These mice were more social and motivated to survive in a forced swim test .
However, a study on rats found that ghrelin activity in the brain caused depressive-like behaviors. These rats were less motivated to survive in a forced swim test .
Most studies, however, agree that ghrelin is associated with anxiety.
Mice injected with ghrelin had higher levels of the stress hormone cortisol and demonstrated anxiety-like behaviors.
Similar results were found in rats with increased ghrelin levels. These rats were less social and avoided open areas .
The more fat you have, the less ghrelin you produce, which is supposed to make you thinner and keep your weight in homeostasis .
Chronically high levels of ghrelin have been shown to increase food intake and promote fat storage in white and brown fat cells .
Chronically high levels of ghrelin promote fat storage and weight gain in mouse models .
In healthy individuals, ghrelin is secreted when the stomach is empty, letting you know when it’s time to eat .
In healthy individuals, ghrelin levels fall after eating to reduce appetite and food intake .
However, in obese subjects, ghrelin levels do not significantly decrease after a meal .
This suggests that for obese and overweight people, ghrelin causes a biased pattern of increased food consumption, decreased energy expenditure, and increased fat storage and weight gain.
Obese and overweight individuals tend to have lower ghrelin levels than healthy individuals, suggesting that ghrelin does not directly contribute to obesity except in patients with Prader-Willi Syndrome whose exceptionally high levels of ghrelin are correlated with obesity and over-eating [62, 63].
High ghrelin levels are associated with conditions characterized by a lack of energy, resulting in weakness and wasting of the body. Such conditions include anorexia, cancer, chronic disease, and chronic failure of the heart, kidneys, and lungs .
When individuals with anorexia nervosa fast, they have higher fasting levels of ghrelin than in healthy individuals. These increased ghrelin levels may be an adaptive response to stimulate eating .
According to some researchers, increased ghrelin levels may indicate the development of ghrelin resistance; that is, the body may be producing normal amounts of ghrelin, but it doesn’t stimulate the appetite. This has been demonstrated in animal models: in mice suffering from cancer-related wasting, ghrelin’s ability to stimulate appetite was reduced .
Ghrelin has been found to counteract muscle and tissue wasting syndromes associated with cancer, heart disease, and chronic disease .
Ghrelin has been found to inhibit the function and reproduction of sex cells in male and female animals. In male animals, high ghrelin levels inhibit sperm production .
In the female reproductive system, high ghrelin levels prevent changes in the uterus that are necessary for fertilization .
This is one mechanism by which calorie restriction may inhibit fertility:
Whether ghrelin contributes to or inhibits the growth and proliferation of cancers is hotly debated. However, most cell studies have found that ghrelin contributes to cancerous growths by promoting cell production and preventing cell death .
Ghrelin may promote the ability of cancer cells to migrate to and invade other parts of the body (to metastasize) .
This spread and growth make cancers difficult to treat, resulting in lower life-expectancy .
In a laboratory study of cancer, blocking ghrelin production in cells reduced the spread of cancer .
Similarly, in humans, fasting-induced ghrelin levels caused people to make riskier economic choices. Normal risk avoidance was restored immediately after eating. The authors suggested that higher ghrelin levels may cause us to make bad decisions .
GHRL Gene (Produces Ghrelin):
GHSR Gene (Ghrelin Receptor):
- RS2232165 (GHSR) GG
- RS2922126 (GHSR) AA
- RS2948694 (GHSR) GG
- RS490683 (GHSR) GG
- RS572169 (GHSR) CC
- RS9819506 (GHSR) TT
Ghrelin levels change throughout the day. They are higher at night and lower during the day .
During the day, ghrelin is highest during a fasting period when the stomach is empty, and lowest right after a meal .
Doctors won’t often order a ghrelin test; there are better and more reliable alternatives for any conditions that might be indicated by high or low ghrelin.
Challenging with ghrelin may help identify growth hormone (GH) deficiency, in particular after aneurysmal subarachnoid hemorrhage. In this test, the patient is given ghrelin intravenously, and their growth hormone levels are monitored thereafter. Because ghrelin strongly provokes GH release, the patient’s response indicates whether or not they have GH deficiency .
Some factors have been associated with increased ghrelin production or release in humans. Increasing (or decreasing) ghrelin may or may not be beneficial to one’s health; your doctor can help you decide what strategies are best for your health. Talk to your doctor before making significant changes to your diet, lifestyle, or supplement regimen.
- Fasting: ghrelin is secreted when the stomach is empty .
- Fiber: in one study, people who regularly eat more fiber in their diets produced more ghrelin under fasting conditions .
- Resistant starch: in a small study of 10 patients, resistant starch intake increased fasting ghrelin levels .
- Zinc: zinc levels in the hair (an indicator of long-term zinc intake) were associated with ghrelin levels in the blood in children .
- Weight loss: ghrelin production decreases as fat mass increases [55, 88].
- Sleep deprivation: even one night of sleep deprivation led to increased ghrelin levels in healthy volunteers. We do not recommend deliberately depriving yourself of sleep for any reason .
- Chronic stress increases ghrelin and appetite .
Likewise, some factors have been associated with decreased ghrelin production or release in humans. Decreasing ghrelin may or may not be beneficial to one’s health; your doctor can help you decide what strategies are best for your health. Talk to your doctor before making significant changes to your diet, lifestyle, or supplement regimen.
- High protein meals [91, 92]: ghrelin levels after eating a high-protein meal were much lower compared to ghrelin levels after a high-calorie meal.
- Adequate sleep 
- Ketogenic diet 
- Acupuncture 
- Vitamin D status: ghrelin was higher in people who were deficient in vitamin D3. This does not necessarily mean that more vitamin D will reduce ghrelin in people who aren’t deficient .
- Honey: when used in place of sugar, honey delayed the ghrelin response in a small study of 14 healthy women .
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