Ghrelin is an important hormone when it comes to health.  It’s not “good” or “bad” but is more dependent on the person.  Ghrelin plays a role in cognitive function, gut function, inflammation, metabolism, weight, fertility and emotional states, to name a few.  See how this hormone pertains to you.

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What is Ghrelin?

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Ghrelin causes weight gain and possibly obesity (R).

Ghrelin is a hunger hormone that stimulates appetite and is mainly produced by specialized stomach cells (RR).

Ghrelin is considered a multi-functional hormone that is also produced by various tissues and organs including the gut, pancreas, kidney, reproductive organs, placenta, bone, and brain (RR2R3).

Injections of Ghrelin in both humans and mice have been shown to increase food intake in a dose-dependent manner: the more Ghrelin, the more you eat (R, R2).

Ghrelin receptors are found in high concentrations in the hypothalamus of the brain and in the pituitary gland (R).

The less body fat we carry, the more ghrelin we produce (R) – a mechanism by which the body tries to increase body weight.

Ghrelin gets released into the blood and goes into the brain, where it sends a hunger signal to the hypothalamus (R).

Ghrelin tells the brain that we don’t have enough energy, that we need to eat, and that we need to conserve our energy (R).

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 (R).

Ghrelin affects the immune system, the reproductive system, strengthens bone, and promotes muscle development (R).

Ghrelin: The Good

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1) Ghrelin Reduces Inflammation

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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 inhibits NF-kB (R) and reduces the production of inflammatory cytokines, such as TNF-α, IFN-γ, IL-6, IL-1α, IL-1β, IL-12, IL-18, IL-17, IL-15 (R).

Ghrelin is needed for immune tolerance. It increases the anti-inflammatory cytokine IL-10 (R).

Ghrelin suppresses Th1-type immune responses and promotes the Th2-type immune response (R).

Indeed, ghrelin exerts anti-inflammatory actions in Inflammatory Bowel Disease (IBD), pancreatitis, sepsis, arthritis, and diabetic nephropathy (RR2).

Ghrelin reduces cell death and increases cell production (R).

Ghrelin protects cells against toxic by-products of oxygen reactions and inflammatory injury (R), which is signaled by pain, heat, redness, swelling, and loss of function (R).

Elderly patients aged 70 and older, who cannot produce as much ghrelin as younger patients, experience more severe disease symptoms (R).

2) Ghrelin Protects Against Autoimmune Disease

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 (R).

Ghrelin protects the lungs, liver, kidneys, and other organs from toxic by-products of oxygen reactions and inflammation injury (R).

Ghrelin has shown potent anti-inflammatory effects in rat and mice models of arthritis, resulting in a slowed progression of the disease (R).

Ghrelin also protects the heart from inflammation injury and improves heart function in mouse models of heart disease (R).

3) Ghrelin Improves Learning and Memory

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Ghrelin produced in the stomach can enter the hippocampus (an area of the brain important for long-term memory storage) through the blood.

In mouse brains, ghrelin changes connections between nerves and cells to enhance learning and memory (RR2).

Similarly, rats injected with ghrelin demonstrated better memory retention (R).

Restricting calorie intake, which has been shown to increase ghrelin levels, improved memory in the elderly (R).

Ghrelin receptors are more concentrated in the hippocampus (R) and ghrelin likely increases hippocampal neurogenesis (R).

Ghrelin increases CREB and BDNF production (R).

Ghrelin enhances neuronal firing (activates NMDA receptor) (R).

Blocking the ghrelin receptor type 1a (GHSR1a) impairs both memory acquisition and memory consolidation (R).

Ghrelin is neuroprotective (R) and activation of the Growth Hormone/IGF-I axis (by ghrelin) is a potential Alzheimer’s treatment (R) and Parkinson’s treatment (R).

4) Ghrelin Activates the Vagus Nerve

Ghrelin stimulates the vagus nerve (R).

Ghrelin stimulates appetite in part via the vagus nerve (R).

Ghrelin increases growth hormone and hunger by stimulating the vagus nerve signal from the brain to the gut, and this is abolished by capsaicin (in chili) (R).

Ghrelin stimulates the pancreas from the brain via the vagus (R).

5) Ghrelin Increases Stomach Acid and Gut Flow

When supplemented, Ghrelin dose-dependently increases stomach acid secretion (R,R2), by a mechanism involving the vagus nerve (R, R2) and histamine synthesis and release (R).

In cells, ghrelin dose-dependently enhances the contraction of stomach muscle cells when stimulated (R).

Several studies have shown a dose-dependent effect of ghrelin on quickening stomach emptying and intestinal transit in rodents. The vagus nerve in part mediates this effect (R).

Ghrelin has been shown to have a series of important therapeutic potentials for the treatment of gut motility disorders, such as constipation (R).

6) Ghrelin Prevents and Treats Heart Disease

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Ghrelin decreases blood pressure in healthy subjects (R).

In animal models with heart failure, ghrelin improved cardiac output (R).

In patients with chronic heart failure, ghrelin improved heart function, increased heart output and increased muscle strength (R).

The mechanisms responsible for the low blood pressure effects of ghrelin include the suppression of fight or flight activity (R), inhibiting the renin-angiotensin system in humans (R) or direct vasodilatory action (RR2).

Acute ghrelin treatment improved survival in a heart attack by preventing an increase in the frequency of heart arrhythmias (rats) (R).

7) Ghrelin Increases Bone Formation

Bone formation is induced by ghrelin.

Ghrelin stimulates bone promoting cells (osteoblasts) and increases bone mineral density, by an unknown mechanism (RR2).

In humans, blood ghrelin level was positively correlated with bone mineral density in peri-, post-, and pre- menopausal women (R).

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 (R).

8) Ghrelin Increases Growth Hormone Release

Ghrelin causes the release of growth hormone by activating the growth hormone secretagogue receptor (R).

The growth hormone secretagogue receptor (GHSR) increases growth hormone release (R).

Many of the benefits of ghrelin come as a result of activating this receptor.

9) Ghrelin Improves the Mitochondria

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Ghrelin increases the production of mitochondria (R).

Ghrelin is a robust activator of mitochondrial function in the hypothalamus (R).

Ghrelin reduces free radicals by increasing UCP2 in the brain (R).

Ghrelin has been shown to stimulate AMPK and SIRT1 (R).

10) Ghrelin Increases Dopamine

In animals, Ghrelin enhanced dopamine release in the hypothalamus (R), amygdala (R), and nucleus accumbens (pleasure center) (R) (via GHSR).

Ghrelin also amplifies dopamine action (via GHSR) (R).

This dopamine release and amplification can increase physical activity (R) and motivation.

Indeed, Ghrelin and its receptor (GHSR) prevents depressive-like behavior (RR2).

Ghrelin: The Bad

1) Ghrelin Affects Mood and Increases Anxiety

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 (R).

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 (R).

Most studies, however, agree that ghrelin increases anxiety.

Mice injected with ghrelin had higher levels of the stress hormone cortisol, and demonstrated anxiety-like behaviors (R)

Similar results were found in rats with increased ghrelin levels. These rats were less social and avoided open areas (R).

2) Ghrelin is Linked to Weight Gain and Obesity

Ghrelin acts as a signal to the brain to induce food intake (R) and enables the storage of surplus calories in fat cells  (R2).

Increased ghrelin is associated with weight loss and fasting (R).

The more fat you have, the less ghrelin you produce, which is supposed to make you thinner and keep your weight in homeostasis (R).

Ghrelin favors the accumulation of stomach fat (R), which in turn favors the formation of liver fat and increases the risk of developing insulin resistance (R).

Chronically high levels of ghrelin have been shown to increase food intake and promote fat storage in white and brown fat cells (R).

Chronically high levels of ghrelin promote fat storage and weight gain in mouse models (R).

In healthy individuals, ghrelin is secreted when the stomach is empty, letting you know when it’s time to eat (R).

Ghrelin has been shown to increase consumption of, and preference for, high-fat foods in mice (R), rats (R2), monkeys (R3), and in people (R4).

In healthy individuals, ghrelin levels fall after eating to reduce appetite and food intake (R).

However, in obese subjects, ghrelin levels do not significantly decrease after a meal (R).

Obese children regain fasting levels of ghrelin more rapidly than healthy children (R).

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 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 (R, R2).

In the liver and fat tissue, ghrelin inhibits AMPK activity (R) and increases PPAR gamma, lipoprotein lipase, and perilipin (R, R2).

4) Ghrelin is Linked to Anorexia Nervosa

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 (R).

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 (R).

Increased ghrelin levels may indicate the development of ghrelin resistance. In mice suffering from cancer-related wasting, ghrelin’s ability to stimulate appetite was reduced (R).

This is because ghrelin treatments have been shown to increase caloric intake in cancer patients with impaired appetite (R), and in healthy volunteers (R).

Ghrelin has been found to counteract muscle and tissue wasting syndromes associated with cancer, heart disease, and chronic disease (R).

5) Ghrelin Can Reduce Fertility

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Ghrelin has been found to inhibit the function and reproduction of sex cells in males and females.

In male animals, high ghrelin levels inhibit sperm production (R).

In the female reproductive system, high ghrelin levels prevent changes in the uterus that are necessary for fertilization (R).

Ghrelin inhibits gonadotropin-releasing hormone (GnRH), LHFSH (R) and progesterone secretion (R), and stimulates of prolactin (R).

Ghrelin also inhibits hCG and testosterone release by testicular cells (RR2).

This is one mechanism by which calorie restriction inhibits fertility.

Calorie restriction—–>higher ghrelin —–>lower testosterone and progesterone.

6) Ghrelin May Contribute to Cancer

Whether ghrelin contributes to or inhibits the growth and proliferation of cancers are debated. However, most studies have found that ghrelin contributes to cancerous growths by promoting cell production and preventing cell death (R).

Ghrelin may promote the ability of cancer cells to migrate to and invade other parts of the body (R).

This spread and growth make cancers difficult to treat, resulting in lower life-expectancy (R).

In a laboratory study of cancer, blocking ghrelin production in cells reduced the spread of cancer (R).

7) Ghrelin Can Influence Decisions

In theory, individuals are willing to take risks when they have little to lose (R). This behavior has been seen in hungry animals that take more risks searching for food when they are running low on energy (R).

Similarly, in humans, fasting-induced ghrelin levels caused people to make riskier economic choices. Normal risk avoidance was restored immediately after eating (R). This shows that higher ghrelin levels may cause us to make bad decisions.

8) Ghrelin Activates the Stress Response

Ghrelin activates the HPA axis and causes a release of cortisol (R).

Genetics of Ghrelin

SelfDecode, the best website for analyzing and decoding genetics from 23andme, has SNPs for ghrelin.

GHRL Gene (Produces Ghrelin):

  1. RS34911341 (GHRL)
  2. RS35683 (GHRL)
  3. RS42451 (GHRL)
  4. RS4684677 (GHRL)
  5. RS696217 (GHRL)

GHSR Gene (Ghrelin Receptor):

  1. RS2232165 (GHSR) GG
  2. RS2922126 (GHSR) AA
  3. RS2948694 (GHSR) GG
  4. RS490683 (GHSR) GG
  5. RS572169 (GHSR) CC
  6. RS9819506 (GHSR) TT

Testing Ghrelin

Ghrelin levels change throughout the day. They are higher at night, and lower during the day (R).

During the day, ghrelin is highest during a fasting period when the stomach is empty, and lowest right after a meal (R).

In 31 healthy controls, the average baseline was 329±32 pmol/l after an overnight fast (R).

In 25 obese subjects, the average baseline was 165±14 pmol/l after an overnight fast (R).

Ways to Increase Ghrelin

If you have low levels of ghrelin and are genetically predisposed to autoimmunity, you might want to increase ghrelin production.

Lifestyle Factors That Increase Ghrelin

  • Weight Loss – Ghrelin is lower in overweight people (R, R2).
  • Sleep deprivation – Even one night of sleep deprivation led to increased ghrelin levels in healthy volunteers (R).
  • Chronic stress increases ghrelin and appetite (R).

Ways to Reduce Ghrelin

If you have high levels of ghrelin, are genetically predisposed to cancer or eating disorders, or are trying to lose weight, you might want to decrease ghrelin production. Here are some habitual ways to decrease ghrelin:

  • Protein (Red meat) – (R, R2) Ghrelin levels after eating a high protein meal was much lower compared to ghrelin levels after a high a calorie meal.
  • Adequate sleep – (R).
  • Fructose Restriction – (R) Ghrelin does not decrease as much after eating fructose. Lingering ghrelin may lead to overeating and contribute to weight gain and obesity.
  • Ketogenic Diet (R)
  • Acute stress has been shown to decrease ghrelin levels and reduce appetite (R).
  • Acupuncture (R)
  • Vitamin D3 (maybe) – Ghrelin was higher in people who were deficient in vitamin D3 (R).
  • Using Honey instead of sugar (maybe) (R).

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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