You and Your Hormones

What is ghrelin?

Ghrelin is a hormone that is produced and released mainly by the stomach with small amounts also released by the small intestine, pancreas and brain.

Ghrelin has numerous functions. It is termed the ‘hunger hormone’ because it stimulates appetite, increases food intake and promotes fat storage. When administered to humans, ghrelin increases food intake by up to 30%; it circulates in the bloodstream and acts at the hypothalamus, an area of the brain crucial in the control of appetite. Ghrelin has also been shown to act on regions of the brain involved in reward processing such as the amygdala.

Ghrelin also stimulates the release of growth hormone from the pituitary gland, which, unlike ghrelin itself, breaks down fat tissue and causes the build-up of muscle.

Ghrelin also has protective effects on the cardiovascular system and plays a role in the control of insulin release.

How is ghrelin controlled?

Ghrelin levels are primarily regulated by food intake. Levels of ghrelin in the blood rise just before eating and when fasting, with the timing of these rises being affected by our normal meal routine. Hence, ghrelin is thought to play a role in mealtime ‘hunger pangs’ and the need to begin meals. Levels of ghrelin increase when fasting (in line with increased hunger) and are lower in individuals with a higher body weight compared with lean individuals, which suggests ghrelin could be involved in the long-term regulation of body weight.

Eating reduces concentrations of ghrelin. Different nutrients slow down ghrelin release to varying degrees; carbohydrates and proteins restrict the production and release of ghrelin to a greater extent than fats.

Somatostatin also restricts ghrelin release, as well as many other hormones released from the digestive tract.

What happens if I have too much ghrelin?

Ghrelin levels increase after dieting, which may explain why diet-induced weight loss can be difficult to maintain. One would expect higher levels in people with obesity. However, ghrelin levels are usually lower in people with higher body weight compared with lean people, which suggests ghrelin is not a cause of obesity; although there is a suggestion that obese people are actually more sensitive to the hormone. However, more research is needed to confirm this.

Prader-Willi syndrome is a genetic disease in which patients have severe obesity, extreme hunger and learning difficulties. Unlike more common forms of obesity, circulating ghrelin levels are high in Prader-Willi syndrome patients and start before the development of obesity. This suggests that ghrelin may contribute to their increased appetite and body weight.

Ghrelin levels are also high in cachexia and the eating disorder, anorexia nervosa. This may be the body’s way of making up for weight loss by stimulating food intake and fat storage.

What happens if I have too little ghrelin?

Gastric bypass surgery, which involves reducing the size of the stomach, is considered to be the most effective treatment for severe, life-threatening obesity. Patients who lose weight after bypass surgery have been found to have lower ghrelin levels than those who lose weight by other means such as diet and exercise, which may partly explain the long-lasting success of this treatment.

Last reviewed: Mar 2018

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Hunger, Fullness, and Appetite Signals

Topic Overview

Listen to your body to tell you when you’re hungry or full.

  • Hunger is a normal sensation that makes you want to eat. Your body tells your brain that your stomach is empty. This makes your stomach growl and gives you hunger pangs. Hunger makes some people feel lightheaded or grouchy. Everyone is different. Hunger is partly controlled by a part of your brain called the hypothalamus, your blood sugar (glucose) level, how empty your stomach and intestines are, and certain hormone levels in your body.
  • Fullness is a feeling of being satisfied. Your stomach tells your brain that it is full. Normally, this feeling causes you to stop eating and not think about food again for several hours. Fullness is partly controlled by the hypothalamus, your blood sugar, and having food in your stomach and intestines.
  • Appetite is a desire for food, usually after seeing, smelling, or thinking about food. Even after you feel full, your appetite can make you keep eating. It can also stop you from eating even though you are hungry. This might happen when you are sick or feeling stressed.

Hormone control of hunger

– Let me ask you a question. Does this gentleman here look hungry or full? Well, we can’t really tell just by looking at his face. We’d have to look at the level of hormones in his bloodstream, because depending on whether this person just ate or not, you’ll have a change in the level of hormones that’ll then talk to your brain to tell you whether you should eat more food or if you’re full. The part of your brain that determines whether you’re hungry or not is called the hypothalamus, the hypothalamus. Your hypothalamus helps make the distinction if your body is rich in energy or if your body is poor in energy. Or, in other words, are you hungry or are you full? Well, imagine we just ate, and the amount of glucose in our blood, or the serum or blood concentration of glucose is high. That means we’re going to release a hormone called insulin. Insulin is released to store the glucose you have in your blood from whatever meal you just ate, and it’ll go and bind receptors in the hypothalamus and block these receptors to indicate to the brain and the hypothalamus that you’re full, you’re not hungry. Now on the flip side, if you have a low blood concentration of glucose, you’re not going to be releasing insulin, and so, you’re not going to be inhibiting the hypothalamus. Now what if we ate a really fatty meal, and we have high levels of lipids or fat in our bloodstream? Something really greasy. Well, that’ll cause the release of a hormone called leptin. Leptin is similar to insulin in that it represents the presence of energy-rich nutrients in the bloodstream. So it’ll go to the hypothalamus and bind receptors there to inhibit the feeling of hunger, which means that when lipid concentration is low, you’re not going to be releasing leptin, and you’re not going to be inhibiting the hypothalamus. Now the final thing that talks to our brain is our stomachs. After we’ve eaten a bunch, our stomach will be pretty full with food, however, if we haven’t eaten in a while, our stomachs can be pretty empty. And I’m sure you’ve had this happen to you. If you’re stomach is empty, it starts talking to you. It starts making noises. It actually starts to growl, and if you listen closely, the stomach is actually saying, ghrelin, ghrelin, which just happens to be the name of the hormone that’s released into the bloodstream to tell the hypothalamus that we are pretty hungry. We’ve got a pretty empty stomach. And instead of a bar, I’ll put a plus sign here to show that the presence of ghrelin will tell the hypothalamus that we’re hungry and motivate us to find some food. These three hormones, insulin, leptin, and ghrelin are the main players that determine whether we’re hungry. One of the interesting things that I should mention, though, about leptin, which I can probably write here, leptin levels rarely change, and the reason why is because leptin levels are based more on the amount of adipose in your body than the amount of lipid you have in your blood, which makes sense because even though we’ll eat some fatty, greasy meal that’ll release lipids into our bloodstream, we’ll definitely have a lot more fat tissue in our body beforehand. So any change in lipid concentration in the blood will be very small relative to how much fat or adipose tissue we have stored in our body.

Why do we get hungry?

It’s 2 hours after breakfast and I’m starting to sense that familiar feeling of hunger pangs, leaving me to wonder: what makes us hungry?

Share on PinterestHow do our brains know when the time for our next meal has come?

Hunger serves an obvious purpose: it tells us that we need to eat to keep our bodies fueled. Yet most of us live in a world where food is ever-present and meals are scheduled around social conventions. Do we really need a reminder to eat breakfast, lunch, and dinner?

Apparently so. While our society may have evolved to provide us with endless opportunities to eat, our bodies are primarily concerned with keeping the well-oiled machine going.

This means that we start to feel hungry once our stomach is empty. However, the sighting of a tasty Halloween treat being shared in the office may tempt us, even though we’re not technically hungry.

That’s because our brains are on the lookout for energy-rich foods, just in case we need to go without later on.

And the key word in this sentence is “brain,” because our gray matter is in charge of hunger.

Hunger and an empty stomach

After a meal, our gastrointestinal tracts slowly empty by pushing food through the stomach and the small and large intestine.

Specialized contractions called the migrating motor complex (MMC) sweep up undigested food, which is a process that takes around 130 minutes. The final phase of the MMC is regulated by a hormone called motilin. Motilin-controlled contractions cause the rumbling in our stomachs and coincide with hunger pangs in humans.

Another hormone implicated in hunger control is ghrelin. In mice, ghrelin activates neurons called agouti-related peptide (AgRP)-expression neurons in the hypothalamus region of the brain, which tell us that we are hungry.

These neurons are the control center for hunger. When AgRP neurons are artificially switched on in mice, they gorge themselves on food.

So, our brains pick up messages from our stomachs and tell us that it’s time for our next meal, occuring around 2 hours after we’ve eaten. But that doesn’t explain the irresistible draw of a delicious snack between meals.

Appealing snacks and the brain

Here, we need to differentiate between homeostatic hunger, which is related purely to balancing our energy reserves short-term, and hedonic hunger, which makes use of opportunities to gather extra energy. Hedonic hunger is less well understood than homeostatic hunger.

When our eyes detect something that we have previously enjoyed eating, our brain is notified.

If we are full, we might take a rain check. However, our brains are hardwired to avoid running out of energy. The offer of extra food can therefore override our feeling of fullness and lead us to grab that tasty snack after all.

How we feel about our previous meal may also have something to do with it.

Medical News Today recently reported on a study that showed that participants who were under the impression that they had eaten a smaller breakfast ate a larger lunch and more daily calories than those who thought that they had eaten a bigger breakfast.

Hunger and overeating

So, our brains control our hunger based on what we eat, whether or not we feel that what we’ve eaten is enough to make us full, and the availability of extra calories.

This system may have worked while humans were hunter-gatherers, but these days, it contributes to overeating and the steady rise of obesity.

Maintaining a healthful diet and weight may therefore be a battle between what we tell our brains and what our brains tell us. In that spirit, I’ve decided to opt for the more healthful Halloween treats.

The biology of hunger

The feeling is all too familiar: a growling in the pit of your stomach that usually starts around late morning when breakfast is just a memory and lunchtime is still a tiny speck on the horizon. It’s hunger – a feeling that begins with the hormone known as ghrelin. Once your body has finished digesting and using up the energy from your last meal, your blood sugar and insulin levels drop. In response to this, ghrelin is produced in the gut and travels to the brain, letting it know that sustenance is needed. The brain then commands the release of a second hormone called neuropeptide Y, which stimulates appetite.

Learn how your hormones modulate your hungry feelings

Once you have answered the call and filled up on a good meal, your stomach gets to work on digestion. Nerves in your stomach sense stretching that lets your brain know you’re full up. Three other hormones also secreted by your digestive system take messages to the brain: cholecystokinin (CCK), GLP-1 and PYY. CCK helps to improve digestion by slowing down the rate at which food is emptied from the stomach into the small intestine, as well as stimulating the production of molecules that help to break down food. GLP-1 tells the pancreas to release more insulin and also reduces appetite. The hormone PYY is secreted into the bloodstream by the small intestine after eating. It binds to receptors in the brain to make you feel full up.

Once all of the food is digested, the blood sugar and insulin levels drop and ghrelin is produced once more, so the hunger cycle continues.

When the mind takes over….

When our bodies tell us we are hungry, it’s an innate reaction – the hormones in our systems let us know of the need for sustenance. But when our minds get involved, it’s a whole different story. There’s not much nutritional value in a bacon sandwich or a frosted cronut, for example, so it’s not a ‘need’ for a treat, it’s a ‘want’. This is because the very first time you experienced a cronut, the mesolimbic centre of your brain (the region that processes pleasure) lit up, as the fatty, sugary goodness of the treat released chemicals known as opioids that bind with receptors in the brain.

This triggers the release of dopamine, the feel-good hormone that makes us happy. It’s actually the same one that is released when we fall in love! Your brain remembers this response, and is encouraging you to munch on that delicious cronut to repeat the pleasurable feeling.

Tucking into a cronut is great at the time, but the pleasure is unfortunately short-lived

For more incredible facts, make sure you pick up the latest copy of How It Works. It’s available from all good retailers, or you can order it online from the ImagineShop. If you have a tablet or smartphone, you can also onto your iOS or Android device. To make sure you never miss an issue of How It Works magazine, make sure you subscribe today!

Plus, take a look at:

The science of hungry: Can being hungry really make you angry?

Can we get addicted to cheese?

How is chocolate made?

When I first heard a friend use the word “hangry” several years ago with a group of friends, I marveled at its accuracy. The portmanteau, a combination of “hungry” and “angry,” perfectly described the present disposition of our buddy Ryan, who was storming ahead of the group, desperately searching for a late night place to eat. We’d just gotten out of a long movie, and Ryan hadn’t eaten since lunch 10 hours ago — a fact he kept repeating to us. He was irritable, impatient and annoyed by our leisurely pace.

Since then I use the word “hangry” all the time (I experience hanger a fair share, myself, to be honest) but I’ve long questioned its scientific authenticity. Is “hanger” a valid phenomenon? Can the physical presence of hunger actually affect our brains and thus our mood, perceptions and reactions? We consulted experts to unpack the fascinating science behind hanger, which is indeed, a real thing.

Hunger turns up the dial on anger

“While it does seem like a silly colloquial term, ‘hanger’ has come about to describe this experience we’ve all had,” says Dr. Kristin Lindquist, assistant professor in the department of psychology and neuroscience at the University of North Carolina, Chapel Hill and co-author of the recent study “Feeling Hangry? When Hunger Is Conceptualized As Emotion”.

“ are interested in this phenomenon because we study emotions and what the more basic processes are in the brain that contribute to emotions. There does seem to be a physiological and corresponding psychological shift when we’re hungry,” she tells NBC News BETTER.

Through a series of tests, Dr. Lindquist and her team concluded that when hungry, people are more likely to be in a negative mindset than those who are sated. One of the tests put participants in slightly annoying situations — like being faced with a computer malfunction and having to start a tedious task over. The empty-stomached participants were overtly peeved, and later, when given an evaluation of the research assistant’s performance were much likely to give negative feedback, saying that the research assistant had “been judgmental towards them”, Lindquist says, “suggesting that hunger turns up the dial on your anger in the face of a frustrating experience.”

Your brain on a diet

March 16, 201802:32

When homeostasis is disrupted, our brain sends signals of a problem

Why does this happen? In part it comes down to interference with the body’s homeostasis, or the body’s sense of equilibrium, that hunger creates.

“Hunger as a state actually causes a lot of shifts in hormones, brain processes and the peripheral nervous system that are comparable to what we see in anger, fear and sadness,” explains Lindquist. “The reason we have emotions in the first place is to help our bodies maintain homeostasis. Your brain is always trying to monitor the body and make sure you’re in homeostasis and if you’re not, it sends a signal to the body that we have to shift some things. That shift out of homeostasis into this state is experienced as negative, cascades of hormones like cortisol, fight or flight responses, and so on. Ultimately your brain is sending a signal to your body that things are not good and need to be figured out.’”

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Hormones and Hunger

“I tried Weight Watchers in middle school. That didn’t work, so I tried starving myself. I’ve tried different over-the-counter diet pills, Slimfast, going to the gym, Weight Watchers again.”

– Jennifer, 36-year-old college student

How many of you have a life story that reads like Jennifer’s? You’ve tried it all – pills, starvation, various diets – but nothing seems to work. When I first met Jennifer, she weighed 323 pounds – down from her highest weight of 350. She could no longer fit into airplane seats, shop at her favorite clothing store, or play softball. Squeezing in and out of her car was almost unbearable. Depressed, tired, and angry, she sought advice from every doctor who would listen to her story. No one could find anything “wrong” with her. Her thyroid tested normal, removal of her gall bladder made things worse, and prescription weight loss drugs made her bloated and jittery. Her weight was interfering with her sleep – she tossed and turned at night, trying to get comfortable, and suspected she might have sleep apnea.

When Jennifer walked into my office, she hadn’t eaten anything that day and it was already noon. She’d been skipping breakfast in hopes that would take the weight off, but confessed that it only lead to 3:00 pm sugar and caffeine cravings that often resulted in binge eating. She complained of daily bouts of nausea, vomiting, and irritable bowel syndrome (IBS). Near tears, Jennifer reflected that all these years she felt like her body was fighting against her.

She was right. Her body – her hormones, in fact – was fighting against her.

I hear these things all the time – heart wrenching stories of weight loss struggles and – most of all – frustration. Maybe you’ve experienced symptoms similar to Jennifer’s. Unstoppable cravings for foods you know aren’t good for you. Irritable Bowel Syndrome. Constant fatigue. Weight gain no matter how hard you try to lose weight: the “shrinking pants syndrome.”

You’re not alone. 85% of all people who diet gain back more weight than they lost – usually within 2-3 years of their initial weight loss. Have you ever wondered what your body’s trying to tell you?

No? Maybe it’s time to start.

When Jennifer stopped to think about it, she realized her body was screaming loud and clear, but she wasn’t heeding its messages. So she kept putting on weight. Why? Jennifer’s body was fighting against her weight loss attempts because her hormones were out of balance. Whenever she went on an extreme calorie diet, her body thought Armageddon was coming and made her store fat in preparation.

The good news is that you can change this. You can learn to work with your hormones rather than against them. You can make peace with food and your body. And you can lose weight. In the coming weeks, we’ll discuss how all of these hormones work and what you can do to achieve hormonal and weight loss, but first we need to set the record straight.

Hormone Hell

In all of Jennifer’s trips to the doctor, the only hormone anyone ever tested was her thyroid hormone. And even then they only checked her thyroid stimulating hormone (TSH). While it is true that irregularities in your thyroid hormone levels can cause a small amount (5-10 pounds) of unexplained weight loss or weight gain, fewer than 5% of Americans suffer from hypothyroidism. With over 50 hormones in the human body, several of which have a direct impact on weight, you’d think hormone levels would be checked more often. Think again.

In truth, like Jennifer, many women seek out assistance from their general practitioner (GP) or family medical doctor when they are having trouble with their weight. While these doctors are fabulous at treating colds and flus, most aren’t trained in helping patients deal with hormone-related weight issues. Nor are they trained in nutrition. Jennifer might have had better luck asking her gynecologist about her weight gain – but at her age (36), they may not have suspected reproductive hormones were to blame.

But maybe they should have. One of the biggest culprits of unexplained weight gain and trouble losing weight in females aged 30-50 is estrogen dominance. In fact, over half of American women suffer from this condition. What is estrogen dominance? Estrogen dominance occurs when you have little or no progesterone to balance the effects of estrogen in the body. It can cause a host of symptoms, including weight gain.

But estrogen isn’t the only hormone to blame. Ever heard of products like CortiSlim? Cortisol is a hormone that is produced when we’re stressed – and who isn’t stressed these days? Cortisol has been blamed for everything from heart attacks to belly fat (especially if you’re on synthetic hormone replacement therapy). You may have even seen infomercials on late night TV for products such as CortiSlim, which promised to “block” cortisol production and make you lose weight. (The makers of CortiSlim actually got sued for false advertising in 2007 and had to retract that claim.) But the idea behind the product wasn’t wrong: cortisol has been linked to weight gain.

Finally, most people aren’t aware that appetite regulation is controlled almost entirely by your digestive hormones: ghrelin, leptin, CCK, and orexin to name a few. What we eat determines when and how those hormones get triggered. Yet, no one ever explains that to us. Hormones cause us to be hungry, but it’s not always because we truly need to eat. Ready to learn how to control your hormones to manage your hunger and lose weight – naturally? Stay tuned next week for your first lesson.

The need to find fuel to generate energy is a profound drive within the biology of all living organisms: we all need food to survive. So it’s not surprising that our bodies have such a complex system to control food intake, driven by hormones.

Hormone levels also change when we lose weight. As much as we battle to trim down via diets and eating patterns, they’re also the reason most of us will regain the weight we lose – or more.

The body’s system for regulating food intake is coordinated by the hypothalamus, which is located under the midline of the brain, behind the eyes:

Within the hypothalamus are nerve cells that, when activated, produce the sensation of hunger. They do so by producing two proteins that cause hunger: neuropeptide Y (NPY) and agouti-related peptide (AGRP).

Quite close to these nerve cells is another set of nerves that powerfully inhibit hunger. They produce two different proteins that inhibit hunger: cocaine and amphetamine-regulated transcript (CART) and melanocyte-stimulating hormone (αMSH).

These two sets of nerve cells initiate and send hunger signals to other areas of the hypothalamus. So, whether you feel inclined to eat or not depends on the balance of the activity between these two sets of neurons.

But what determines which set of neurons dominates at any given time?

The activity is mainly controlled by hormones that circulate in the blood. These come from tissues in various parts of the body that deal with energy intake and storage, including the gut (which receives and digests the food), the fat (which stores the energy) and the pancreas (which makes hormones that are involved in energy storage, such as insulin).

Hormones in the blood

Let’s take a closer look at how each of these blood-circulating hormones work.

Ghrelin is made in the stomach. It stimulates hunger by entering the brain and acting on the neurons in the hypothalamus to increase the activity of the hunger-causing nerve cells and reducing the activity of hunger-inhibiting cells. As the stomach empties, the release of ghrelin increases. As soon as the stomach is filled, it decreases.

Insulin-like peptide 5 (ILP-5) was found to stimulate hunger in 2014. It is the second circulating hormone to have this effect and is mainly produced in the colon. But we still don’t know its physiological role.

Cholecystokinin (CCK) is produced in the upper small bowel in response to food and gives a feeling of fullness. It is released soon after food reaches the small bowel. Researchers have found CCK can stop a mouse from eating as soon as it’s injected into the brain.

Peptide YY, glucagon-like peptide 1 (GLP-1), oxyntomodulin and uroguanilin are all made from the last part of the small bowel and make us feel full. They are released in response to food in the gut.

Leptin is the most powerful appetite-suppressing hormone and is made in fat cells. It was discovered in 1994. The more fat cells we have, the more leptin the body produces.

Amylin, insulin and pancreatic polypeptide are made in the pancreas. Studies in the United States have shown that when insulin enters the brain it inhibits hunger, telling the brain “there is enough energy in the body, take a rest”.

Amylin, discovered in 1981, is made in the same cells that make insulin (the beta cells). It has been shown to inhibit food intake.

The exact role of pancreatic polypeptide is not yet known, but there is evidence that it inhibits hunger.

The hypothalamus also receives signals from pleasure pathways that use dopamine, endocannabinoids and serotonin as messengers, which influence eating behaviour.

Once full, the stomach reduces the desire to eat both by lowering ghrelin production and by sending a message to the hypothalamus. Ghrelin levels reach a low around 30 to 60 minutes after eating.

Levels of hormones that make us feel full – CCK, PYY, GLP-1, amylin and insulin – all increase following a meal to reach a peak about 30 to 60 minutes later.

All the hormones then gradually return to their fasting levels three to four hours after a meal.

How weight loss affects our hormones

Several studies have found that diet-induced weight loss is associated with hormone changes that, together, promote weight regain.

Following weight loss, leptin levels decrease profoundly. Other hormonal changes include increases in circulating ghrelin, GIP and pancreatic polypeptide and reductions in PYY and CCK. Almost all of these changes favour regaining lost weight, by increasing hunger, reducing satiety and improving the capacity to store fat. These hormonal changes seem to be present for at least one year after weight loss, leading to a persistent increase in hunger.

These findings suggest suppressing hunger after weight loss – preferably with a replacement of hormones – may help people maintain their new weight.

Several of these agents have recently been approved by different regulatory bodies in the United States, Europe or Canada, but only one – liraglutide – is a version of one of the naturally occurring appetite suppressants (GLP-1). The ideal medication to maintain weight loss would be a long-acting mixture of three or more of the blood-circulating hormones we examined above: leptin, amylin, GLP-1, PYY, CCK and oxyntomodulin.

But producing such a mixture is proving a considerable challenge, so researchers continue to investigate how this might be done.

This article is part of an occasional series, Chemical Messengers, on hormones and the body.

Ghrelin, the “Go” Hormone

by Ted Kyle, RPh, MBA, and William Hignett

Fall 2011

To view a PDF version of this article, click here.

What if we could, for one day, create our bodies and change them as we please to improve our physical nature? How would we enhance our strengths and address what we see as problems? How would we change our bodies and minds to alleviate stress, anxiety and physical problems? Related to weight, we would probably make it easier and very straightforward to lose pounds and fat and to keep the weight off our bodies.

If we had this power, we might consider simplifying hormonal actions that fuel and curb hunger so these actions are clear-cut and we comprehend exactly how to lose weight. In fact, in real life, two hormones do appear to be this direct in their actions on eating and weight. Ghrelin (grell-in) is the hunger hormone and leptin is the stop appetite hormone. Many believe that the actions of these “go and stop” appetite hormones are straightforward, and that one is bad and the other is good.

Ghrelin, the “Hunger Hormone”
Ghrelin is responsible for stimulating hunger, and it is the “go” hormone that tells you when to eat. As the “hunger hormone,” some may be ready to make ghrelin out to be a villain. Obesity and weight-loss are complicated, so perhaps it would be comforting to have a bad guy hormone that stimulates hunger so we can focus on this “bad” hormone that causes us to gain weight.

Interesting Fact
What exactly is meant by saying ghrelin is the hunger hormone? The ghrelin hormone, discovered in 1999, is released primarily from cells in the stomach and travels to the brain. There, it interacts with both the hypothalamus (the brain’s physiological eating center) and the brain’s pleasure centers to arouse hunger.

Throughout the course of a day, ghrelin levels naturally change dramatically, rising steeply before a meal and then plummeting after eating. Ghrelin stimulates the brain, which leads to an increase in appetite, and it slows metabolism and decreases the body’s ability to burn fat. Ghrelin also favors the amassing of fatty tissue in the abdominal area. In experiments, people who got injections of ghrelin before a buffet meal ate 30 percent more than a group of eaters not given extra ghrelin.

Like many things in life, it is not as apparent as it seems that ghrelin is a hunger hormone and therefore bad. Consider, for example, that ghrelin levels in the blood of individuals affected by obesity are lower than those in leaner individuals. That finding is opposite to expectations that obesity would be due to excess levels of the hunger hormone. It has also been discovered that individuals suffering from anorexia have high blood levels of ghrelin compared to both the thin and normal-weight controls.

The findings suggest that ghrelin is inversely related to calorie intake. Other studies have found that individuals who lose weight and try to keep it off make more ghrelin than they did before losing weight, as if their bodies are fighting to regain the lost fat. An explanation for these findings is that excess weight may increase sensitivity to ghrelin. For example, there may be more receptors in those affected by obesity for the hormone, so not as much ghrelin is needed to stimulate hunger.

Leptin, the “Stop Appetite Hormone”
The opposing hormone to ghrelin is the stop appetite hormone, leptin. Leptin is a hormone produced in the fat cells. It plays a role in regulating body weight by signaling the brain to reduce appetite and burn more calories. Leptin is a primary modulator of body weight and metabolism, and it mediates weight-loss by decreasing hunger and food consumption and increasing energy expenditure. Yet, some studies have shown that losing weight causes a marked decrease in leptin levels, which may in turn increase appetite.

Counter to what would be anticipated, obesity is linked to unusually high concentrations of leptin. Some research suggests that these high concentrations make the receptors for leptin inactive and impair the very mechanism that should eliminate excess fat. Then, although plenty of leptin is produced, the body’s appetite suppression system is unable to function properly.

Ghrelin Blockers as a Weight-loss Treatment
If ghrelin stimulates hunger, wouldn’t a ghrelin inhibitor (antagonist) be effective in helping people lose weight? Several pharmaceutical companies have or are conducting research on such a compound. The Scripps Research Institute in California in 2006 successfully developed an anti-obesity ghrelin vaccine that significantly slowed weight gain and reduced body fat in animals. It is possible that in the future there will be a ghrelin blocking medication. But, since ghrelin also makes eating food more pleasurable, a drug blocking the brain’s pleasure centers might create side effects related to mood regulation.

The research on ghrelin blockers is no slam dunk. Take as an example the promising medication, rimonabant, which works by interfering with one of the brain’s cannabinoid receptors and successfully causes weight-loss. However, rimonabant also affects the pleasure center in the brain and side effects include the potential for severe depression, sometimes leading to suicide. This drug was not approved for use due to these side effects.

Conclusion
Finally, what is not known is how important the role ghrelin plays in everyday eating and weight gain/loss. More research is needed before firm conclusions can be drawn about the effects of ghrelin. But, if we could create our bodies for one day, perhaps we’d simplify the actions of ghrelin and leptin and overcome the appetite stimulating effects of the “hunger hormone.”

Beyond this wish, the reality is that the human body has a complex system of hormones that interact in countless ways. Therefore, we are not likely to find a simple one-to-one relationship between these hormones and weight, or that ghrelin and leptin are likely part of a chain of physiological processes; too bad. We could use a villain when considering the challenges of obesity.

About the Authors:
Ted Kyle, RPh, MBA, is a pharmacist and health marketing expert. He is a member of the OAC National Board of Directors.

William Hignett is a disease management expert with a master’s degree in public health from the University of Pittsburgh. He has years of experience as a health educator for universities, hospitals, Fortune 100 companies and health insurers.

Leptin, ghrelin, and weight loss. Here’s what the research has to say.

It’s a grim statistic: Most people who go on a diet and lose weight end up regaining that weight within a year.

Doesn’t sound too promising.

Why does this happen? Well, there are many reasons.

The big one is that people view a “diet” as a short-term solution and don’t really change their behaviours — which is why our Precision Nutrition Coaching program focuses on sustainable, permanent change.

Another reason is that our bodies have appetite- and weight-regulating hormonal mechanisms that try to maintain homeostasis (aka keep things the same) over the long haul. When we consistently take in less energy (in the form of food) than we expend through basal metabolism and activity (as in a diet or famine), our bodies respond by making us hungrier.

Our bodies don’t generally want to change. They like everything to stay the same. If we try to change things, our bodies will respond with compensation mechanisms, such as revving up our appetite hormones.

Two important hormones that shape our appetite and hunger signals are leptin and ghrelin. Let’s find out more about leptin, ghrelin, and weight loss.

Hormonal control of appetite and body fat

Leptin and ghrelin seem to be the big players in regulating appetite, which consequently influences body weight/fat. When we get hungrier, we tend to eat more. When we eat more, obviously, we maintain our body weight or gain that weight back.

Both leptin and ghrelin are peripheral signals with central effects. In other words, they’re secreted in other parts of the body (peripheral) but affect our brain (central).

Leptin is secreted primarily in fat cells, as well as the stomach, heart, placenta, and skeletal muscle. Leptin decreases hunger.

Ghrelin is secreted primarily in the lining of the stomach. Ghrelin increases hunger.

Both hormones respond to how well-fed you are; leptin usually also correlates to fat mass — the more fat you have, the more leptin you produce. Both hormones activate your hypothalamus (a part of your brain about the size of an almond).

And here’s an important point: both hormones and their signals get messed up with obesity.

Ghrelin and leptin act on the brain via the hypothalamus (from Kojima & Kangawa, 2006).

Leptin

Back in 1994, researchers noticed that one genetically altered strain of mouse ate a lot and was obese. When researchers administered a new substance, leptin (from leptos, or “thin” in Greek), the mice lost weight.

Soon after, nearly everybody interested in fat research was doing research on leptin.

At the time this was the holy grail of obesity research: a protein that made really, really fat mice into skinny mice. Fantastic! We’ll just make leptin pills, and everyone will be ripped, including the mice.

Well, like most things in biology, leptin is more complicated than that.

As it turns out, leptin injections only worked on mice (and people) who were genetically leptin deficient — only about 5-10% of obese subjects. The other 90-95% were out of luck.

How does leptin work?

Leptin is made by adipose tissue (aka fat) and is secreted into the circulatory system, where it travels to the hypothalamus. Leptin tells the hypothalamus that we have enough fat, so we can eat less or stop eating. Leptin may also increase metabolism, although there is conflicting research on this point. (1)

Generally, the more fat you have, the more leptin you make; the less food you’ll eat; and the higher your metabolic rate (possibly). Conversely, the less fat you have, the less leptin you have, and the hungrier you’ll be.

Basically, for weight loss — the more leptin the better.

Leptin resistance

You’d think, then, that fatter folks would somehow magically stop eating or start losing weight once their leptin levels were high enough. Unfortunately, you can become leptin resistant (2).

In that case, you can have a lot of fat making a lot of leptin, but it doesn’t work. The brain isn’t listening. No drop in appetite. No increased metabolism. Your brain might even think you’re starving, because as far as it’s concerned, there’s not enough leptin. So it makes you even hungrier.

It’s a vicious cycle.

  1. Eat more, gain body fat.
  2. More body fat means more leptin in fat cells.
  3. Too much fat means that proper leptin signalling is disrupted.
  4. The brain thinks you’re starving, which makes you want to eat more.
  5. You get fatter. And hungrier.
  6. You eat more. Gain more fat.
  7. And so on.

Leptin resistance is similar to insulin resistance (and they also share common signalling pathways). Insulin resistance occurs when there’s lots of insulin being produced (for example, with a diet high in sugar and simple carbohydrate), but the body and brain have stopped “listening” to insulin’s effects.

Interestingly, both types of resistance seem to occur together in obese people, though obese men who tend to have more internal belly fat (visceral fat) have higher insulin levels, and women who tend to have more fat under their skin have higher leptin levels (2).

Another leptin resistance fun fact is that fructose seems to induce leptin resistance (3).

There are a few possible explanations for how leptin resistance actually works. One theory is that leptin can’t get to the hypothalamus because the proteins that transport it across the blood brain barrier aren’t working or aren’t there, since there’s a buildup of leptin in the cerebral spinal fluid that bathes the brain (4).

Regardless of the actual mechanics, the important point here is that past a certain level, having more body fat can screw up your appetite signals and actually make you hungrier.

Ghrelin

Ghrelin was discovered 7 years after leptin, but after the leptin letdown, there was much less fanfare.

Leptin is a hormone that is a result of a buildup of fat, so it’s a long term regulator of body weight. Meanwhile, ghrelin is the short term Hey I’m hungry when do we eat? regulator.

Your stomach makes ghrelin when it’s empty. Just like leptin, ghrelin goes into the blood, crosses the blood-brain barrier, and ends up at your hypothalamus, where it tells you you’re hungry (1,5).

Ghrelin is high before you eat and low after you eat.

If you want to lose weight you want less ghrelin, so you don’t get hungry. If you want to gain weight, say if you’re scrawny, then you want more ghrelin — or at least you want it to stay high as you eat, so you’ll want to eat more.

Both hormones, as I mentioned, regulate appetite and hunger, and both of them regulate homeostasis — in this case, keeping you adequately fed. When you try to lose fat, your body will probably respond by changing hormone levels so that you get hungrier.

Obviously, this presents a challenge for folks trying to lose fat and keep it off — leading, perhaps, to the dreaded “yo-yo dieting” phenomenon.

Research question

Can leptin and ghrelin levels provide some explanation for the ups and downs that dieters experience? And could this relationship be more complicated than we expect?

This week’s review looks at how leptin and ghrelin levels are related to weight regain after dieting. (The title kind of gives the punch line away.)

Crujeiras AB, Goyenechea E, Abete I, Lage M, Carreira MC, Martínez JA, Casanueva FF. Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels. J Clin Endocrinol Metab. 2010 Nov;95(11):5037-44. Epub 2010 Aug 18.

Methods

Researchers put over 160 obese and overweight men and women with an average BMI over 31.1 kg/m2 on a calorie restricted diet for 8 weeks.

This diet was 30% less (500-600 kcal/day) than the participants’ total energy expenditure, with 15% of calories from protein, 30% from fat and 55% from carbohydrates. There was no change in physical activity, just less food.

Researchers measured body weight, body fat and waist girths. They also took blood samples. Measures were taken before dieting (week 0), right after the dieting (week 8), and 6 months later (32 weeks).

Results

After 8 weeks on the diet, people lost an average of 5% body weight. Men lost 5.9% on average, and women lost 4.5%. They lost an average of 1.6% body fat and 4.1 cm off their waists.

Gainers and losers

But the average doesn’t give us the whole story. Some folks lost more than 5% of their weight, while others lost less. This may seem self-evident and not that interesting… until you look at their blood samples.

Dieters who lost more weight (>5%) had a bigger drop in leptin and insulin compared to dieters who lost less weight (<5%). Somehow losing weight is correlated to drops in leptin and insulin.

Figure 1 below compares the differences between the two groups. Compared to the <5% weight loss group, the >5% weight loss group:

  • lost more weight (obviously)
  • had lower leptin levels
  • had lower insulin levels
  • had higher ghrelin levels

Figure 1: Differences between >5% and <5% weight loss groups

This is pretty much what you’d expect.

Six month after the diet ended, this split continued. About half the group lost more weight; half the group re-gained the weight they lost.

Blood levels of leptin and ghrelin were correlated to weight loss or regain — and this effect often depended on sex.

  • Women with lower blood leptin at the end of dieting were more likely to maintain their weight loss, but ghrelin didn’t seem to make a difference.
  • Men with higher ghrelin levels at the end of dieting were more likely to regain weight, but leptin didn’t seem to matter.
  • For both men and women, insulin levels at the end of dieting didn’t seem to matter in the long term, although insulin levels did increase when weight went back up.
  • For both men and women, ghrelin levels were higher (meaning they were hungrier) at the end of dieting, but in weight losers, ghrelin levels dropped.

Huh.

Figure 2 shows the changes in hormone levels between weight maintainers (WM) and weight regainers (WR) at the start of the diet (0 weeks), end of the diet (8 weeks), and 6 months later (32 weeks). WRs are indicated by the red lines; WMs are the black lines with circles.

Figure 2: Hormone levels in weight maintainers (WM) and weight regainers (WR), by sex

Discussion and conclusion

The biggest hurdle dieters face is weight regain — and dealing with it is a daunting prospect.

Appetite is controlled by a host of complex, interacting factors. This study suggests that the hormonal mechanisms may be different for men and women — and among men and women.

This difference may reflect the different hormonal environments in men and women. For instance:

  • Ghrelin seems to be affected by growth hormone release, which differs in men and women.(6)
  • Leptin seems to influence reproduction and fertility in women, which is related to women’s body fat levels. Women appear to be much more sensitive than men to leptin levels… unless men are given estrogen.(6)
  • Intranasally administered insulin makes men less hungry and lose weight, but makes women hungrier and gain weight… unless women’s estrogen levels, or men’s testosterone levels, are low.(6)

However, there were also important differences within groups as well. Some men lost weight while others regained it. Some women lost weight while others regained it.

As the researchers point out, these findings suggest “the existence of two different populations according to the leptin and ghrelin levels influencing the response outcomes”.

We’d expect that folks who regain weight easily would have lower leptin and higher ghrelin — making them hungrier. Not so in this study. The researchers propose that these results “are consistent with a disruption in the sensitivity to these hormone signals, probably in the central nervous system of those subjects with a higher predisposition to regain body weight.”

This suggests that in obese people, leptin and ghrelin signals may not always work in ways that we expect. Obesity can disrupt normal appetite signalling.

There is probably more to the story, and we’ll need more research to understand all the elements of weight loss.

Many factors in weight loss

Thus it appears that there are many important factors that shape successful weight loss.

If you’re looking for the silver bullet that will magically kill hunger and strip body fat off you, give up now.

Metabolic endocrinology appears to be only slightly more complicated than a nuclear reactor and brain surgery combined. No single hormone controls body composition, appetite, and hunger — and your individual hormonal profile may be relatively unique.

What’s also notable is that dieters who lost more weight on the diet had more significant changes in their appetite. They were probably hungrier while losing that weight.

Does the diet matter?

A few things that likely are contributing to weight regain are that this was a diet. Reduce calories for 8 weeks, lose the weight, then hope things work out for you. Obviously since it worked for some people, this method has some merit.

But as the data show, short-term diets alone don’t have a great success rate in the long run.

The macronutrient breakdown of this diet could also be relevant. It’s relatively low in protein, moderate in fat, and high in carbohydrate. We might see different hormonal effects with, say, a low-carb, high-fat, high-protein diet. (See last week’s Research Review on high-protein diets if you want to know more.)

What else can I do?

Strictly looking at improving ghrelin and leptin levels, some studies have shown that taking fish oil and getting regular sleep help. (7-9)

Other factors that help long term weight loss include:

  • increased physical activity
  • getting social support
  • behaviour change techniques (e.g. goal-setting) (10).

Bottom line

Many interacting hormones shape our appetite and hunger. Several factors affect these hormones and our response to them.

So if you’re looking for a single solution — or rely on a short-term diet as a quick fix — you’ll probably be disappointed.

But there’s good news: There are many things that you can do that will lead to lasting body composition change.

  1. Take fish oil. Omega 3 fatty acids are linked to decreased hunger. (7)
  2. Sleep. Lack of sleep leads to more ghrelin and less leptin, as well as disrupted glucose and insulin metabolism. (8,9)
  3. Don’t get discouraged by these kinds of studies. Other research shows that it is possible to lose weight and keep it off — you just have to do a bit more than pop a leptin pill or do a few jumping jacks. The National Weight Control Registry tracks the features of successful losers. These include behaviour change, a commitment to good nutrition, and regular exercise.
  4. Understand that when losing fat, you might be hungrier. That’s normal.
  5. Enrol in the PN Coaching program. We’ve helped thousands of folks lose weight and keep it off for good. (And if you’re already in Lean Eating, congratulations! You’re well on your way!)

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How to Control Your Hunger Hormones to Lose Weight and Keep It Off

A symphony of factors control hunger, fullness, and ultimately our weight, including everything from how well you slept last night to the accounts you follow on Instagram. Also involved in the complex process are hormones, particularly the two that are often referred to as hunger hormones, leptin and ghrelin.

In an ideal world, leptin and ghrelin work together to help keep you at a healthy weight. In the real world, well, 70% of the population ends up overweight or obese. Could out-of-whack hormones be to blame?

To answer that question, you first have to understand how the so-called hunger hormones work.

Leptin is the satiety hormone. Essentially, it tells you when to stop eating. “It makes you feel full, and it blocks appetite,” says James Shoemaker, MD, PhD, associate professor in biochemistry and molecular biology at St. Louis University.

Ghrelin, on the other hand, tells you when you’re hungry and need to eat. Think of it as the gremlin making your stomach grumble. “It’s made in the stomach primarily, and it’s released when you haven’t eaten for a while,” says Michael Schwartz, MD, co-director of the Diabetes Institute at the University of Washington in Seattle. Ghrelin peaks every four hours or so–roughly corresponding to breakfast, lunch, and dinner.

RELATED: How to Reprogram Your Appetite to Crave Healthy Foods

When everything’s running smoothly, the two hormones work in harmony, says Philadelphia-based Marjorie Nolan Cohn, RDN, a spokesperson for the Academy of Nutrition & Dietetics. “As one is rising, the other one is dropping.”

But things can–and do–go wrong.

For starters, leptin levels fluctuate with how much fat you have. When you lose weight, leptin levels drop. With less of that appetite-suppressing hormone, you end up feeling hungrier and eating more, potentially causing you to gain back the weight you had lost. “ you have returned to your baseline weight, leptin will have recovered,” explains Dr. Schwartz.

In fact, a study that looked at 14 former Biggest Loser contestants showed that, indeed, leptin levels declined in those who lost large amounts of weight (they lost an average of almost 130 pounds). That could explain why most of them regained much of the weight over time.

It’s also possible to become desensitized to leptin–called leptin resistance–if you are constantly stuffing yourself with food. “You’d think that if you’re eating a lot you shouldn’t be hungry, but it’s the opposite,” says Cohn, who is also author of The Belly Fat Fix: Taming Ghrelin, Your Hunger Hormone, for Quick, Healthy Weight Loss. “Even though there may be leptin in circulation, it’s not registering,” she says, and you don’t know you’re full.

RELATED: 11 Foods That Make You Hungrier

Hunger-stimulating ghrelin levels also vary with weight loss. After dieting, ghrelin production increases, potentially causing people to eat more and gain weight. “The cravings can be so hard to control,” says Cohn. “Once you’re out of whack, it’s really hard to get back into balance.”

Why our bodies fight back

Understandably, human beings are designed to fight starvation. Part of the body’s response to dieting is a drive to revert to whatever weight we were previously. “As you gain weight, the brain thinks that the new weight is the one that’s supposed to be regulated,” says Dr. Schwartz. “That’s why it’s so hard to lose weight and keep it off.”

That response typically kicks in after you’ve lost around 5% to 7% of your bodyweight, he says. “Once you lose more than 5% of your bodyweight, on average, you’re going to engage these responses that counter-regulate against the weight loss. Whether you do it quickly or slowly, it doesn’t matter very much.”

Interestingly, people who undergo bariatric surgery seem to have lower levels of hunger-promoting ghrelin than people who take pounds off through plain old diet and exercise. This may be why weight loss after gastric bypass surgery tends to last for longer periods of time.

Harnessing your hormones

Barring surgery, is there any way you can control these hormones to your advantage? Luckily, yes.

If you can, stick to a more moderate weight loss of just around 5% of your bodyweight so you don’t trigger that debilitating drop in leptin. Then, readjust mealtime: “Eat on the clock,” says Cohn. That means every two hours if you like to eat smaller portions or every four hours if you eat larger meals. This draws down stomach-grumbling ghrelin levels.

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It’s also important to eat a balance of foods at each meal, particularly protein and complex carbs. “Protein is a major player in suppressing ghrelin,” Cohn says. “It takes more work to digest and keeps you full longer.” Fiber also slows digestion and helps keep you full, she adds. Look for complex carbs like whole grains, veggies, and fruit, especially those containing a type of fiber known as “resistant starch,” like not-quite-ripe bananas.

Exercise may also help control your hunger hormones so you can shed pounds for good. One study found that losing weight on a treadmill resulted in lower ghrelin levels than slimming down by simply eating less.

4 Ways to Outsmart Hunger Hormones

Sluggish afternoons, vending-machine cravings, and a growling stomach (even though you just had lunch) can pack on the pounds and erode willpower. But tackling those healthy-eating hurdles may be about more than just self-control: What and when 
you eat is also determined by hormones-which are, in turn, infuenced by both your biology and your behaviors. Here’s how to harness four of the biggest players in your internal hunger games.

RELATED: The Best Carbs for Weight Loss

Hunger Hormone: Leptin

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Named for the Greek word leptos, meaning “thin,” leptin is produced by fat cells and released into the bloodstream as you eat. When the body functions properly, it tells you when to stop eating. Overweight people, however, can produce excess leptin and may develop resistance to chronically elevated levels. Their brains ignore the satiety signals, leaving them hungry even after meals.

Make it work for you: Regular exercise-especially moderate- to high-intensity interval training-can help keep leptin levels functioning properly, according to a study from Tehran University in Iran, as can getting seven to eight hours of sleep
a night. For people with leptin resistance, research shows that electroacupuncture (which uses needles that carry a small electric current) may help lower levels and suppress appetite.

Hunger Hormone: Ghrelin

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Leptin’s counterpart, ghrelin, is known as the appetite hormone; when leptin levels are low-as in, when you haven’t eaten in a while-ghrelin levels are high. After a meal, ghrelin levels drop and usually stay low for several hours while you digest food.

Make it work for you: The same habits that help control leptin-sleep and daily exercise-can keep ghrelin in check. One study, published in the journal Clinical Science, also found that diets high in protein suppressed ghrelin longer than high-fat diets. The over-the-counter weight-loss supplement Vysera-CLS ($99 for a one-month supply) may also help keep ghrelin levels from rebounding temporarily-as well as help to prevent blood-sugar spikes- after meals, promoting feelings of satiety.

Hunger Hormone: Cortisol

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This stress hormone is produced as part of the body’s fght-or-fight response during times of physical or emotional trauma. It can provide a temporary boost of energy and alertness, but it can also trigger high-carb, high-fat cravings. When levels are continually elevated, it also causes calories to be stored around the middle, contributing to dangerous (and hard-to-lose) belly fat.

Make it work for you: The best way to keep cortisol at bay? Chill out. Research shows that relaxation techniques like meditation, yoga, and listening to soothing music reduce stress hormones. Or, consider a quick fx: In one study from the University College London, stressed-out people who regularly drank black tea had cortisol levels 20 percent lower than those who sipped a placebo drink; in another from Australian researchers, those who chewed gum had levels 12 percent lower than those who didn’t.

Hunger Hormone: Estrogen

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Sex hormones fluctuate throughout the month, depending on your cycle and whether you’re using hormonal birth control. In general, estrogen is at its lowest on day one of your period. It climbs for two weeks, then takes a dive in weeks three and four of your cycle. Falling estrogen causes serotonin levels to drop and cortisol to rise, so you may feel cranky and hungrier than usual-which can lead to bingeing, especially on fatty, salty, or sugary foods.

Make it work for you: Indulging PMS- related cravings won’t improve symptoms, so help balance out your hormone levels- and satisfy your appetite-with complex carbs like whole-wheat pasta, beans, and brown rice.

  • By Shape Editors

According to endocrinologists from the VU University Medical Center in Amsterdam, two of the most important hormones to focus on for natural weight loss and energy balance are ghrelin and leptin. (1) Many experts call ghrelin and leptin the “hunger hormones” because they work to either increase or decrease our appetite. (2)

Although certain weight loss programs involving taking artificial hormones — such as those that use human chorionic gonadotropin (HCG) to increase fat-burning — can be dangerous, there are safe and effective steps we can take to manipulate our natural hunger hormones and help us reach our weight-loss goals.

It might feel like the cards are stacked against you when it comes achieving sustainable weight loss, but it’s important to understand that we have a great deal of control over our hormones, as they reliably respond to dietary, exercise and stress-related changes we make. We don’t need to resort to unnatural, harmful methods to lose weight fast and reach our ideal weight — instead we need to focus on setting up a healthy food environment that encourages nutrient-dense eating, managing stress, moving our bodies consistently and making smart food choices long-term.

What Is Ghrelin?

Ghrelin is an appetite-increasing hormone, given its name because it is considered to be a “growth hormone-releasing peptide” (or GHR). Since ghrelin makes you feel hungry, it makes sense that levels tend to rise before meals and fall after meals. How is ghrelin secreted? It’s made in the stomach and fluctuates throughout the day depending on your intake of food. As a peptide hormone, it’s produced by ghrelinergic cells located in the gastrointestinal tract, which communicate with the central nervous system, especially the brain.

Once produced in the stomach, rising levels of ghrelin sends a signal to the brain that causes you to feel hungrier. Regarded as the only appetite-stimulating hormone in humans, ghrelin is one of the main contributors in giving people the “munchies” and potentially causing them to overeat.

What is ghrelin’s effect on growth hormone and metabolism?

Ghrelin and related growth hormone secretagogues increase body weight and fat mass. One way they do this is by triggering receptors in a part of the brain called the arcuate nucleus, which controls leptin and insulin sensitivity. Ghrelin can sometimes override signals sent from the GI tract to the brain that tells you to stop eating, such as those caused by gastric distension (pressure placed on the stomach as it expands). Ghrelin also seems capable of contributing to cellular changes, including alterations in endothelial cells lining the blood vessels. (3)

According to research published in the journal Addiction Biology, ghrelin reduces fat utilization and is a vital component of the food reward cascade controlled by the brain’s pleasure-reward system. (4) Ghrelin levels are negatively correlated with weight, so dieting (especially severe calorie restriction) tends to increase ghrelin output. Ghrelin has been found to play a major role in inducing short-term feeding and long-term weight gain, but the hormone also has other roles, including influencing: (5)

  • Regulation of growth hormone and insulin secretion
  • Glucose and lipid metabolism
  • Gastrointestinal motility
  • Blood pressure and heart rate
  • And neurogenesis (the process in which neurons are generated from neural stem cells)

In addition, more ghrelin is released directly in response to stressful situations, explaining why so many people have the tendency to eat when they’re stressed. By perpetuating the stress cycle, ghrelin contributes to weight gain by maintaining a person’s stress levels and causing strong urges to snack or overeat.

What is the difference between leptin and ghrelin?

Ghrelin and leptin work together to facilitate feeding, energy balance and weight management. Leptin is a hormone that is made by fat cells that decreases your appetite. It essentially does the opposite of ghrelin, which increases appetite. Both hormones play a role in body weight maintenance. Within the brain the same area that holds the receptors for ghrelin (called the ghrelin/growth hormone secretagogue receptors, or GHS-Rs) also holds the receptors for leptin.

Because the body produces leptin based on body fat percentage, weight gain causes your blood leptin levels to increase. The opposite is also true: weight loss will result in decreased levels of leptin (and often more hunger). Unfortunately, overweight and obese people are generally believed to be “leptin-resistant,” which contributes to further weight gain and difficulty losing excess weight because they require more food to feel “full” or satiated. However, there is still a lot to learn about how leptin-resistence and increased ghrelin may contribute to obesity. (6)

To summarize ghrelin’s main roles, here are three points to remember:

  1. Ghrelin is a fast-acting hormone that plays a vital role in increasing appetite, meal initiation and contributing to weight gain.
  2. Ghrelin works with another hormone called leptin to manage body weight. Leptin usually mediates long-term regulation of energy balance because it suppresses appetite and food intake, thereby inducing weight loss (although not in the case of obesity).
  3. Both hormones can be controlled naturally, primarily through making smart dietary choices, exercising, sleeping enough and stress management.

Related: Lipase: the Digestive Enzyme that Fights Major Diseases

How to Make Ghrelin, Your Hunger Hormone, Work for You

How can you lower your ghrelin levels? Here are six steps to take in order to reduce ghrelin and gain control of your appetite:

1. Don’t Overly-Restrict Calories (AKA Attempting “Crash Diets”)

Levels of ghrelin will increase if you’re consistently under-eating, which is one reason why dieting makes most people feel pretty hungry. On the other hand, overeating causes ghrelin levels to decrease, but this shouldn’t be the goal either (unless you’re trying to gain weight).

The fact that being in calorie-deficit makes you feel hungrier is one of the most challenging things about attempting to diet for weight loss. Fortunately, however, it’s been found that certain types of dietary habits can help to control ghrelin — including eating lots of nutrient-dense, unprocessed foods and eating enough fiber and protein.

Ghrelin levels should go down significantly following a meal, and stay down for about three hours or more before you begin to start feeling hungry again. If you notice yourself getting hungry soon after eating, or frequently wanting to snack throughout the day, consider if you’re eating enough calories in general. It’s possible you can afford to increase your intake of protein, healthy fats, or fiber from complex (unrefined) carbohydrates if you’re severely restricting one of these macronutrients. Eating enough healthy food to sustain your activity level and feel energized will prevent you from entering or staying in “starvation mode” that will only increase your appetite.

2. Eat Enough Protein

Even when someone is restricting their calorie intake, eating a higher proportion of protein foods can help control their appetite.

A 2006 study published in the American Journal of Clinical Nutrition that focused on the effects of a high-protein meals on postprandial ghrelin response states that “The most satiating macronutrient appears to be dietary protein.” When study participants ate a high-protein breakfast, they experienced decreased postprandial ghrelin concentrations more strongly over time compared to when they ate a higher-carbohydrate breakfast.

The researchers found evidence that the high-protein meals had an effect on glucose-dependent insulinotropic polypeptides, which mediated the ghrelin response. In addition, the high-protein meals were more effective at slowing gastric emptying, which prolongs feelings of fullness. (7) Other studies point to similar findings about how protein may contribute to weight loss: protein tends to ward off hunger, prevent loss of muscle mass during dieting, increases secretion of satiety hormones, increases the thermic effect of food digestion and improves glucose homeostasis. (8)

3. Exercise, Especially Burst Training and High Intensity Interval Training (HIIT)

For years, generic weight-loss advice given by most health care providers focused on low-to-moderate aerobic activity, such as walking or running 30–60 minutes every day. Research from the past decade continues to report that ghrelin increases (and therefore appetite goes up) and also that leptin decreases after these types of exercises, making this notion obsolete.

Instead of doing “steady state cardio,” burst training is one of the best ways to manage hunger and eating behavior to burn belly fat and to manipulate ghrelin and leptin to improve the odds of weight loss. Burst training can also increase muscle mass, which means when you do eat more you’re better able to use the extra calories without gaining fat.

In a study conducted by the University of Bath (U.K.), various hormone levels in individuals who participated in a form of burst training (i.e., 30-second sprint on a cycle ergometer controlling for low or high intensity) showed that:

  • Total ghrelin concentrations declined after high-intensity sprinting and were significantly lower after 30 minutes of recovery than they were pre-exercise, suggesting that burst training can not only contribute to weight loss, but help curb appetite long-term. (9)
  • Growth hormone (attributed to weight loss) concentrations were greater in the high-intensity than in the low-intensity group, suggesting that burst training affects other hormones in addition to ghrelin. (10)

The Journal of Sports Science recently published similar results regarding burst, high-intensity exercise and blood soluble leptin receptor (sOB-R) concentrations. (11) Findings link low levels of sOB-R to obesity because having less receptors to receive the hormone prevents leptin from attaching to cells, which negates its hunger-curbing and weight-loss effects. After evaluating 18 healthy male volunteers who completed either a low-intensity or high-intensity exercise routine, researchers discovered that:

  • At 24 hours post-exercise, the high-intensity group had significantly higher sOB-R concentrations and significantly lower leptin concentrations than the low-intensity group; this suggests that burst training is more effective at not only increasing the cell’s sensitivity to leptin, but also the overall blood levels of the hormone.
  • Additionally, leptin levels at 48 hours post-exercise were also significantly lower for the high-intensity group, suggesting that burst training, like ghrelin, has long-term effects on weight loss that are beneficial long after your workout.

These are just two examples from a myriad of research studies that prove high-intensity interval training is not only most effective at curbing appetite and controlling weight gain in the short term, but also in the long run.

4. Get Good Sleep (Early to Bed, Early to Rise, So You Can Work Out!)

Getting enough sleep (usually about 7–9 hours per night for most adults) is associated with better management of ghrelin and leptin. Sleep deprivation was shown in one study involving 12 young men to be associated with an increase in ghrelin levels, appetite and hunger compared to when the men slept for longer periods (up to 10 hours a night). (12)

To best maximize your exercise routine (especially if your workouts are intense), and best control ghrelin and leptin, research shows that it’s a good idea to exercise first thing every morning if possible. According to a study published in the Journal of Physiology, exercising on an empty stomach may improve glucose tolerance and insulin sensitivity, which are both tied to ghrelin production. (13)

In addition to contributing to type 2 diabetes prevention and weight loss, exercising early in the day is known to help regulate appetite, especially curbing the munchies and the desire to eat unhealthy snacks. One study published in the Asian Journal of Sports Medicine found evidence that “morning exercise may cause greater levels of satiety in comparison with afternoon exercise.” (14)

5. Practice Stress Management

In addition to making dietary changes and getting enough exercise, it’s important to turn your attention to the level of stress you’re dealing with. The journal Obesity Reviews recently published an article evaluating the effects of combined exercise, sleep and stress management on hormones. Researchers from the study concluded that “Behavioral interventions could offer a practical, cost-effective method for reducing or stabilizing ghrelin levels after initial weight loss to improve weight loss maintenance.” (15)

In other words, the stress cycle must be stopped to first reach your weight-loss goals and then to effectively maintain a healthy weight over time. Chronic stress is likely to increase your appetite, especially for “comfort foods”, and contribute to other unhealthy habits like overeating, snacking, not making time to cook at home, possibly drinking more alcohol, skipping sleep and remaining more sedentary.

One suggestion is to wrap up your day on a positive note by practicing Tai Chi or yoga in the evenings, which helps set the tone for a good night’s sleep and also preps your body for your morning workout the following day. There are many ways to help manage stress, but ultimately different techniques will work for different people. Meditation, prayer, writing in a journal, spending time outdoors, sustaining positive relationships, getting enough rest and downtime, and eating an anti-inflammatory diet are some of the best ways to keep your stress levels down and reverse the vicious weight-gain stress cycle.

6. Avoid “Highly Palatable” Processed Foods

Foods that have been refined and processed to taste exceptionally great are usually high in calories and also often low in nutrients. These are called “highly palatable” foods by obesity and nutrition experts (or sometimes “ultra-processed foods and drinks”, or UPFDs), because they tend to cause overeating due to how they activate reward centers in the brain. (16)

Normally when we eat a meal chemical/hormonal messages are sent from our digestive tract to our brain and various other parts of our body to tell us we’ve had enough and stop eating. But research suggests that when we have the opportunity to eat highly-processed, calorie-dense foods, this feedback system doesn’t work so well. Essentially it seems that the human brain is “hard-wired” to seek out and enjoy calorie-dense foods, so including many of them in your diet interferes with appetite regulation.

What types of foods tend to increase appetite and risk for overeating the most? Examples include: (17)

  • Cakes, donuts, cookies, pastries, brownies and other sweets
  • Soda and sweetened beverages
  • Pizza
  • White bread, rolls, wraps, pita, etc.
  • Chocolate, candy and ice cream
  • Salty snacks like chips, pretzels and French fries
  • And fried foods

It’s easy for us to overcome calories and remain “hungry” when we eat foods high in refined grains, added sugar, added fat and synthetic ingredients, especially when these tempting attributes are combined together. Eating a whole-foods diet on the other hand — including one with lots of veggies, fruit, proteins like eggs or fish, healthy fats like avocado or coconut, etc. — is the best way to naturally regulate your appetite since these foods are high in volume, high in fiber, lower in calories, higher in nutrients, and overall make you more capable of turning down your desire to keep eating.

Related: IIFYM (If It Fits Your Macros) Guide to Lose Weight

Precautions Regarding Hunger Hormones & Weight Loss

While I do recommend taking steps to naturally balance levels of ghrelin or leptin, I’d warn against attempting other weight loss programs that involve the use of artificial hormones.

Manipulating hormones in order to boost weight loss is not a new concept. In the 1950s, medical and scientific communities began suggesting artificial hormone therapy to help people lose weight. Topping the list of these weight loss programs is one of the most controversial and hotly debated gimmicks: the use of human chorionic gonadotropin (HCG), a hormone produced during pregnancy that helps release a woman’s fat stores in order to support the growth of her baby.

HCG stimulates the hypothalamus to start fat metabolism, which provides nutrients for the baby. Remove the baby from the equation and those fat-turned-nutrients need somewhere to go. The HCG diet supposedly helps men and women achieve “miraculous” weight loss through a combination of taking HCG and following a diet restricted to just 500–800 calories per day. Basically, this is a starvation diet. The theory behind this misguided use of hormone therapy is that the extra adipose tissue (fat) released in the bloodstream supplements the calories people aren’t consuming each day, helping dieters lose up to two pounds per day. Sadly, ever since Dr. Oz openly changed his mind about HCG and aired a special report on it in 2012, more people are on the diet than ever before.

According to the Mayo Clinic, two important facts are crucial to understanding this type of hormone therapy for weight loss:

  1. The HCG diet is not safe and doesn’t work long-term, as most people will regain the initial weight that they lose.
  2. The Food and Drug Administration has actually advised people “to steer clear from over-the-counter weight-loss products that contain HCG.” (18)

Final Thoughts on Ghrelin

  • Ghrelin is an appetite-increasing hormone that makes you feel hungry before meals, but decreases after meals so you feel more satisfied.
  • Ghrelin works with another hormone called leptin to manage hunger, food intake and body weight. Ghrelin increases hunger, while leptin (secreted by fat cells) decreases hunger.
  • Both hormones can be controlled naturally, primarily through making smart dietary choices, exercising, sleeping enough and managing stress.

Hormone that tells you you re full

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