Hormone Series Part 7: Ghrelin, the 'Hunger' Hormone.

Ghrelin is often referred to as the hunger hormone. As the name suggests, when ghrelin levels become elevated, this is a signal for the body to increase food intake. Dysregulation of the pathways that influence ghrelin production and how the body responds to ghrelin have been associated with weight gain. There are many factors that can influence our body’s production of Ghrelin and in this article we will take you on a little whistle stop tour of what this hormone is, what it does and how it is influenced by the foods we eat and how this determines feelings of fullness and hunger.


Ghrelin’s name comes from its capacity to stimulate the releases of growth hormone (GH + ‘relin’ which means release = ghrelin!) Ghrelin is released in many of the body’s organs but as a hunger hormone, it is probably unsurprising that around 75% of circulating ghrelin is produced in the stomach. Ghrelin is a peptide hormone, meaning it is made up of long chains of amino acids, and like GH can be converted to different active forms after its release; the most important of these is a product called acyl ghrelin (AG).


AG has a strong appetite stimulating effect and therefore its release has a profound effect on metabolism by governing calorie intake. Importantly, AG also has a direct effect on the creation of new fat cells and increased amounts of fat storage, meaning that dysfunction of ghrelin can lead to increased hunger and calorie intake which causes a vicious circle of weight gain which also then causes further dysfunction and the cycle continues. Weight loss improves ghrelin release and response, but unfortunately this is a bit cart before the horse in the sense that when someone loses weight, it takes a while for ghrelin (and other metabolism regulating hormones) to catch up, meaning that, at least for a while, weight loss will always be associated with hunger for a majority of people.


Interestingly, exercise doesn’t appear to increase appetite to the same levels that a restriction in calories does; this is linked to the mechanisms that cause ghrelin release. Therefore, it is important for those starting out at losing weight to increase expenditure as opposed to overly restricting calories, which is something that unfortunately is an approach that many people take and can be setting themselves up for failure. Exercise also leads to increased fitness, which in turn leads to increased output. From this perspective, the role of exercise in weight loss is often misunderstood and understated.


Ghrelin exerts its effects on appetite by interacting with the hypothalamus, stimulating the release of neurotransmitters and neuropeptides, which are important signallers that cause its hunger-inducing (orexigenic is the scientific name for this) effects as well as inhibiting the release of signallers that supress appetite having anorexigenic (‘without appetite’) effects.


The appetite increasing effects of AG also influence the pathways by which the body uses both fats and carbohydrates as a fuel source, and therefore it is unsurprising that not just the amount of food we eat, but the nature of the food that we eat can influence our levels of hunger and how full we feel from the foods we eat. Despite high levels of circulating ghrelin being associated with obesity, its effects are to actually increase the use of fatty acids as a fuel source meaning that ghrelin, despite its negative associations with weight gain, is theorised more likely to be an important protector against starvation and the use of glycogen and muscle tissue as a fuel source, helping preserve muscle and energy for high demand activities which is important from an evolutionary perspective.


The total amount of ghrelin present in the body is related to body mass index (BMI), with higher ghrelin levels associated with lower BMI, this is unsurprising when you considering the hunger suffered by those suffering with malnutrition and anorexia nervosa. In overweight people there tends to be a lower level of ghrelin compared to normal people, however in certain conditions overweight people can have higher circulating levels of leptin, and this can have obvious implications for rapid and ever-increasing weight gain as hunger is never satisfied.



More recent research is starting to show that the different forms ghrelin takes after release need to be considered more than by just the total amount in circulation. Interestingly, although released as response to food, ghrelin can also be released in preparation for the consumption of food in an anticipatory manner, especially with regimented eating patterns. This could mean that to control hunger, it is important to be consistent with eating patterns so the anticipatory increases in ghrelin are kept under control, regardless of what nutrition strategy you employ.



Despite ghrelin’s associations with hunger and fullness, it is interesting that these relationships are not as cut and dry as one may think. The distention we feel from feeling full can play a role in our perception of hunger, however it also appears the composition of foods is equally, if not more important. In animal and human models, dietary fats reduce ghrelin levels to a lesser extent than amino acids and carbohydrate, which is surprising as fat is often considered a more filling macronutrient than carbohydrate, although this is likely to be dependent on both the type of fat and carbohydrates that are eaten. When comparing beverages of equal volume and calories, carbohydrates, although in the short term recue ghrelin, have a ‘rebound effect’ effect a few hours later, stimulating appetite; therefore when we consider carbohydrate feedings, regular intake every few hours ‘might’ be of benefit, but this will of course be influenced by carbohydrate type, the amount of fat and protein in each meal as these also impact on digestion and absorption processes.


Detection of nutrients in the digestive tract have shown these have comparable structural features to our cells that detect taste.



Ghrelin interacts with many hormones; alongside stimulating GH release, it has an inverse relationship with insulin – as insulin increases, ghrelin typically decreases. This is unsurprising as insulin levels rise after eating, so we would expect hunger levels to fall, although the exact mechanisms by which these interact is not understood in its entirety and is likely to include a variety of other hormones and signallers in both the digestive tract and brain to regulate energy homeostasis, including having opposing effects to leptin that appear to interact and regulate each other, depending on both immediate energy available from food intake and the levels of our energy reserves that combine to determine calorie consumption, or at least the want to consume calories! Every person who has dieted for a physique contest or to low levels of body fat knows that even after consuming a large amount of calories in a meal, or even over the course of a few days, when the body should get ‘full’, the capacity to over eat to ‘fill up the tanks’ is massive and many people will eat to severe distension of the stomach but still feel hungry! This may not cease for a number of weeks after a contest before the body’s energy stores are sufficiently high. This is one of the challenges for those who want to stay lean year round and for many of us this is just not possible, as the body wants to maintain a certain level of body fat as part of our innate survival adaptations.


So if getting to single figure body fat is your goal, then at some point you will get hungry and suffer severe cravings to go alongside the fatigue, tiredness and lack of performance both in and out the gym (sounds fun doesn’t it?) On a final note, it is ill advised for most people to try and stay very lean year round as this can disrupt hormonal function, metabolism and in extreme cases put your health at risk and is something that should only be attained for short periods before returning to healthy levels of body fat. Of course this will differ from person to person, but understanding your own body and where it ‘fits’ in terms of healthy body fat levels is important to figure out in order to maintain your progress in the gym, sustain a social/work life and most importantly be healthy.