Episode 2 - The Biochemistry of Hunger

I want to start our journey through the biochemistry of nutrition with the biochemistry of hunger. Because we do not have the ability to photosynthesize energy like plants we have to eat to survive. Our brains have a lot of information to process each day and in order to ensure that we continue to feed our body food we have lots of redundant systems that make us hungry.

The Chemistry of Hunger:

Hunger is an experience that comes from a complex network of neurological and endocrine signaling. Meaning our automatic brain (the part of our brain that we cannot control) and body communicate with hormones (our endocrine system); that communication is then interpreted by our conscious brain as hunger, thirst, fatigue, etc.

This communication system in our body is guided by the interplay of our genetics and our environment. Our environment is more than the location we live, it is includes the stress in our lives, our sleep patterns, the food that we eat, the air that we breathe, the water we drink, it is everything that we interact with in our lives.

One of the primary drivers for our feeling of hunger comes from our blood sugar and our gastrointestinal transit time (medical term for how long it takes food to travel through your digestive system). This is because our brain uses glucose (sugar) for energy if the sugar in our blood is too low we feel bad (light headed, shaky, cranky) and if the sugar in our blood is too high we feel bad (but we usually do not feel high blood sugar). One of the ways our body regulates how much sugar is in our blood is through converting sugar into storable substances like glycogen and triglycerides these substances then get stored in our fat, muscle, and organs, when we need to increase our blood sugar without eating we can convert that stored glycogen and triglycerides back into sugar. Our liver can store glycogen and convert it to glucose quickly and that is how we can sleep overnight without needing a snack. Our body can turn the fat and protein we eat into sugar as well, which is just to say that our body is very good at getting what it needs out of our food.

Our body has this reflexive system of hormone communication to control our blood sugar – telling us to eat to replenish our blood sugar and glycogen stores. The hormones Insulin and Glucagon are hormones that react to our blood sugar and are reflexive; meaning they are independent of our brain. Insulin takes sugar from our blood and takes it to our cells; Glucagon goes to our cells and tells them to release sugar and fatty acids. These hormones are release by our pancreas.

Additionally this system is complicated by other hormones which come from our fat cells such as leptin; ghrelin and somatostatin from our stomach; NPY from our brain. Don't worry there will not be a quiz after, I only mention these hormone names because they are being talked about in pop culture and I want to give you some accurate information about them. These hormones are actively being studies because of their role in our hunger signals. For example, NIH has funded studies demonstrating that gastric bypass surgery is able to eliminate the ghrelin secreting cells from the stomach, which is one of the reasons this surgery is so successful. For all of us self-hackers, I have not been able to find how an individual can modulate they are neuroendocrine hormone signals at home. There have been studies that show how many things that we eat or drink can affect our hunger levels, such as caffeine and fiber. However, the effect of anything on our hunger is short lived because we adapt to that intervention. Meaning that over time we have a physiological adaptation to that substance and over a period of time will eliminate the benefit, meaning it is not a permanent change to our hormones.

One reason I wanted to talk about hunger is because it is a challenge to overcome hunger as we try to change what we eat. Because of how hard it is to control our hunger fad diets try to capitalize on eliminating or reducing hunger. These diets focus on highly restrictive eating which preventing us from responding to habituated eating vs. hunger driving intake. The success of these diets is that they create a deficit; but they fail over time because the restrictive pattern of eating is unsustainable.

Our Environment + Behavior affect our hunger

Hunger can be habituated; this is called the motivational state of hunger; when we are driven to eat by habit, sensory input (smell, cravings), or convenience vs. actual physiological demands. Many studies have looked at what triggers us to confuse organic hunger (hunger coming from our need for food) with olfactory or habituated eating stimuli and there is currently no consensus on how to extinguish unnecessary hunger.

There have been many studies looking at meal frequency to modulate hunger. The recommendation to eat 3 meals and 2 snacks comes from years of data (below) showing that frequent meals decrease the amount of ghrelin released and therefore help us not feel ravenous at each meal. In contrast to that, there is a recent surge in data supporting intermittent fasting, this is a situation where we can see the data coming out appear to be in contradiction to our recommendations. I want to note that it is not a contradiction, we are all individuals and that makes it impossible for us to create a single diet recommendation that will work for everyone. The reason we recommend the 3 meals and 2 snacks is because the data supporting it is very good and it is a safe place to start for the vast majority of people.

Data around hunger:

• A 2014 metanalysis from the American journal of clinical nutrition supports the notion that eating rate affects energy intake; specifically a slower eating rate was associated with lower energy intake with a standardized mean difference between groups of .45; meaning there was a 45% energy intake difference between groups with a 95% confidence interval; meaning there is a 5% chance that these results are due to change alone. Altering eating rate was not shown to alter subjective reports of hunger at meal end or 2–3.5 h later. Their analysis proposes the following mechanism “chewing may influence various satiety hormones, altering concentrations of insulin, glucagon-like peptide 1, cholecystokinin, peptide YY, pancreatic polypeptide, and triglycerides (26, 28, 29, 32). In addition, eating rate could also influence food intake via differences in stomach distension, with slow eating resulting in slower gastric emptying”

• A 2015 metanalysis in physiology and behavior supports that prolonged chewing influences appetite and food intake; with self-reported hunger being lower in groups who chewed significantly; with 3/5 studies showing that the increased number of chews per bite increasing relevant gut hormones linked to subjective satiety. The data was influenced by the fasting period between meals; the greater the fasting period; with shorter fasting periods being linked with greater lower hunger ratings after eating – no duh. Because Ghrelin, an appetite hormone is elevated in the fasting state and suppresses response to food intake. This is why you may feel hunger that is out of proportion to reality if you have not eaten for a long time and is the foundation for the “many meals per day” theory to control hunger.

• A meta-analysis in in eating frequency and overweight and obesity in children/adolescents in 2013 AAP showed that higher eating frequency was associated with lower body weight status in children/adolecents = meaning eating lower calorie but more frequent meals decreases overall intake. And a 2015 meta-analysis in frontiers in nutrition stated that “the hypothesis that increased eating frequency may influence energy intake continues to be sustained in the literature."

• 2016 meta analysis in international journal of environmental research and public heath echoed this sentiment “increased eating frequency may lead to a lower obesity risk but higher energy intake.”

I encourage you to try 5 meals a day; or 3 meals and 2 snacks (3+2) per day because that has the most convincing data demonstrating decreased hunger hormones and then if you find that too challenging or not helpful try an intermittent fasting or decreased meal frequency program. In case you are interested I have included the below studies on intermittent fasting (I do not endorse intermittent fasting, it is just an example of the opposite to the 3+2 meal frequency):

• This meta-analysis on intermittent fasting dose not effectively answer what the effects of intermittent energy restriction are in the long term.

• This meta-analysis on intermittent fasting shows that intermittent fasting is more effective than no treatment

• This meta-analysis shows that there is a slight reduction in fasting insulin was evident in Intermittent Fasting

Individuality also extends to differences between men and women. There are studies that accumulated data suggesting that certain dietary interventions are more successful in men vs women. For example, the Mediterranean diet intervention led to greater improvements in dietary intakes in men than women; which contributed to the metabolic changes seen improved in men; but this is also because the metabolic profile found in men at the start of the study was worse than women. Most studies do not have parallel men vs women analysis and thus make generalizations based on only the sex studied which is a significant pervasive flaw.

So at this time it’s important to recognize that physiological hunger is a basic drive to meet our calorie demand and that through the incorporation of a well-balanced diet with plenty of carbohydrates (fiber, fruits, vegetables, whole grains), protein, fat, and water; the majority of people will feel full and appropriately hungry at the right frequency and duration to meet their metabolic needs. In situations where hunger is beyond adequate diet & exercise interventions it would be appropriate to talk with your physician about a further evaluation.

Behavior patterns matter:

The hunger behavior feedback loop can lead us to feel hungry based on environmental cues which are completely separate from our internal system (need for calories). Just like any other habit loop hunger can have power for relationships to our everyday activities. So to keep this simple when we think about The hunger signals we need to tune in to our body. This means when you feel hunger where do you feel it? Do you feel it in your stomach, or do you have symptoms of low blood sugar like being lightheaded or irritable? Hunger can be confused with boredom and habit loops. For example, if you always eat the moment you come home from work you may always feel hungry every time you come home. Likewise if you always get breakfast at the same fast food restaurant off the highway you might feel hungry every time you pass that exit. If you find that your hunger is associated with boredom or with a stimulus such as a specific exit on the highway, the best way to reset your hunger signals is to create a new habit loop. So that when you were bored you find a new reward or when you pass that exit on the highway you find any reward that is not associated with food and those new rewards allow you to stop associating those external stimuli with hunger.

Fatigue and hunger:

Fatigue is usually associated with a low energy state energy being calories. Therefore, mental and physical fatigue are evolutionary associated with increasing hunger signals through neuroendocrine hormones. This is why when people have very exhausting jobs, high stress lives, or high training schedules hunger can feel immense. Hunger due to fatigue is the most challenging to overcome, because it is hunger that is disproportionate to our actual calorie need. When hunger is increased by life stress or by exhausting work (work that is not increasing caloric burn), de-stressing activities such as meditation, low intensity exercise such as walking or easy yoga, and journaling or reflection exercises have had the most meaningful impact. That is obviously easier to say than to do, and it is a very long process of incorporating mindfulness and relaxation into ones life while still dealing with life stress. We get told all the time in medical school to incorporate these and relaxing activities and it is beyond challenging to add such tasks to an already busy schedule. So be kind to yourself when you start tackling the stress in your life.

Some additional resources:

Biochemistry of hunger - CELL

https://www.sciencedirect.com/science/article/pii/S0092867415002615

behavioral susceptibility to obesity – CELL

https://www.sciencedirect.com/science/article/abs/pii/S0031938415300226

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