Ghrelin hormone and food intake, influence on hunger by Ray Sahelian, M.D.
October 24 2014

Ghrelin hormone is a brain-gut peptide hormone with two main physiological actions: growth hormone secretagogue activity and food intake inducer. Ghrelin is produced in the gut and triggers the brain to promote eating. Although its production is prevalently gastric, ghrelin is widely expressed in several tissues, where it might therefore act as a paracrine or autocrine factor. Ghrelin is much more than a simple growth hormone secretagogue. Ghrelin has other activities including stimulation of pituitary hormones secretion, modulation of food intake and control of energy metabolism, regulation of gastric and pancreatic activity, and cardiovascular and hemodynamic activities. In addition, modulation of cartilage and bone homeostasis, sleep and behavioral influences, and modulation of the immune system, as well as effects on cell proliferation, are other relevant actions of ghrelin. Thus, ghrelin peptide appears to be an important component of an integrated multifaceted regulatory system.
   Ghrelin levels increase before meals and decrease after meals.

Ghrelin is a 28 amino acid peptide mainly produced by a subset of stomach cells and also by the hypothalamus, the pituitary, and other tissues. It exerts wide physiological actions throughout the body, including growth hormone secretion, appetite and food intake, gastric secretion and gastrointestinal motility, glucose homeostasis, cardiovascular functions, anti-inflammatory functions, reproductive functions, and bone formation.

Hunger hormone
Ghrelin is the only known orexigenic (a substance that increases appetite) hormone. It is involved in mealtime hunger and meal initiation. Circulating ghrelin levels decrease with feeding and increase before meals, achieving concentrations sufficient to stimulate hunger and food intake. Before eating, surges occur before every meal on various fixed feeding schedules and also among individuals initiating meals voluntarily without time- or food-related cues.
   Ghrelin is thought to be the counterpart of the hormone leptin, produced by fat tissue. Leptin induces satiation when present at high levels. Sleep deprivation increases morning plasma concentrations of this hunger-promoting hormone.

Q. I read the article but please let me know which product will stimulate my appetite best.
   A. Besides marijuana, I am not aware of any potent natural appetite stimulant.

Where is it found?
Ghrelin, the appetite stimulating hormone, has been identified from a number of different species including humans, rat, pig, mouse, gerbil, eel, goldfish, bullfrog and chicken. A peptide with ghrelin-like activity has also been found in certain plants.

Protein in diet suppresses ghrelin
Diets high in protein are a good way to keep hunger in check. Protein in the diet is effective at keeping ghrelin in check, while carbohydrates and fats don't work that well. Suppression of ghrelin is a way to lose appetite. Fats suppress ghrelin quite poorly. Proteins suppress ghrelin quite well. Carbohydrates suprress ghrelin well at first, but levels rebound later, rising to an even higher level. Carbohydrates eventually make people even hungrier than before they had eaten.

Ghrelin makes you feel good
Tests on rats show that the appetite hormone ghrelin acts on pleasure receptors in the brain. In mice and rats it triggers the same neurons as delicious food, sexual experience, and many recreational drugs; that is, neurons that provide the sensation of pleasure and the expectation of reward. "These neurons produce dopamine and are located in a region of the brain known as the ventral tegmental area (VTA). Horvath's team found that ghrelin, itself only discovered in the last decade, acts on a molecular structure on brain cells called the ghrelin receptor growth hormone secretagogue 1 receptor or GHSR for short. When ghrelin is infused into this area of the rats' brains, they eat as hungrily as they did after being kept hungry overnight.

Glucomannan supplement and ghrelin
Immediate and long-term effects of glucomannan on total ghrelin and leptin in type 2 diabetes mellitus.
Diabetes Res Clin Pract. 2009. Chearskul S, Kriengsinyos W, Kooptiwut S, Sangurai S, Onreabroi S, Churintaraphan M.
Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Effects of glucomannan as a supplementary treatment in type 2 diabetes mellitus were investigated by measuring ghrelin, leptin and insulin responses to OGTT. Glucomannan enhanced prandial ghrelin reduction when given before glucose load and impeded the rise of fasting ghrelin after 4-week supplement. Ghrelin-induced feeding may be attenuated by glucomannan.

Improved appetite
In a small study of frail older women with unexplained weight loss, infusion of ghrelin led to improvement in appetite and was well tolerated. The study, conducted at the University of Pennsylvania School of Medicine in Philadelphia, involved five women aged 70 or older who had lost more than 5 percent of their body weight without intending to do so, and who met at least two other clinical criteria for frailty, and five healthy control women. The study findings were presented at The Endocrine Society's annual meeting in Washington, D.C. in June 2009. Each woman received two three-hour infusions, one week apart, of ghrelin or inactive solution (saline). Overall, women consumed 51 percent more calories after receiving the ghrelin infusion than after the saline. With ghrelin, the women ate more carbohydrates and protein, but the same amount of fat, Dr. Anne Cappola and colleagues reported.

Research
J Psychiatr Res. 2013. Ghrelin suppresses nocturnal secretion of luteinizing hormone (LH) and thyroid stimulating hormone (TSH) in patients with major depression. Major depression is associated with various endocrine disturbances. Apart from the well-known hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, also the function of the hypothalamic-pituitary-gonadal (HPG) axis and of the hypothalamic-pituitary-thyroid (HPT) axis may be altered compared to healthy subjects. The orexigenic hormone ghrelin is involved in mood regulation and may have antidepressant effects. In addition, it has been shown to suppress secretion of luteinizing hormone (LH) and thyroid stimulating hormone (TSH) in healthy subjects.  Ghrelin suppressed nocturnal secretion of LH and TSH in patients with major depression. However, these effects were weaker than previously shown in healthy subjects.

Effect of a high-protein breakfast on the postprandial ghrelin response
American Journal of Clinical Nutrition 2006.
The most satiating macronutrient appears to be dietary protein. Few studies have investigated the effects of dietary protein on ghrelin secretion in humans. This study was designed to investigate whether a high-protein (HP) breakfast is more satiating than a high-carbohydrate breakfast (HC) through suppression of postprandial ghrelin concentrations or through other physiologic processes. Fifteen healthy men were studied in a single-blind, crossover design. Blood samples and subjective measures of satiety were assessed frequently for 3 h after the consumption of 2 isocaloric breakfasts that differed in their protein and carbohydrate content (58% of energy from protein and 14% of energy from carbohydrate compared with19.3% of energy from protein and 47% of energy from carbohydrate). Conclusions: The HP breakfast decreased postprandial ghrelin concentrations more strongly over time than did the HC breakfast. High associations between ghrelin and glucose-dependent insulinotropic polypeptide and glucagon suggest that stimulation of these peptides may mediate the postprandial ghrelin response. The HP breakfast also reduced gastric emptying, probably through increased secretion of cholecystokinin and glucagon-like peptide 1.

Additional gut hormones
Food intake and bodyweight are regulated by the brainstem, hypothalamus and reward circuits. These centers integrate cognitive inputs with humoral and neuronal signals of nutritional status. Gut hormones and enzymes include pancreatic polypeptide, peptide YY, amylin, glucagon-like peptide-1, oxyntomodulin, cholecystokinin and ghrelin.

Questions
My brother 49 years old started to get a dialysis on May 5,2007. Since than he lost almost half of his weight ( from 85 kg to 47 kg). After each session of this dialysis he could not eat for a day, even he did, he eat like a baby. To top it up, during his dialysis, his usually weight lost is in the range of 0.5-3 kg. In the July 2005 issue of the Journal of the American Society of Nephrology, I learned that hormone ghrelin might help to boost food intake. I talked to his doctor about it, he said that he never heard about it and doesn’t have any desire to do any investigation.
   I am not aware of ghrelin hormone being available as a prescription drug. Would Marinol be helpful to increase appetite? I am not sure.