Friday, December 7, 2012

Myths, Metabolism, & Appetite Part 3

Part 3-Appetite
In part 1 and parts 2a and 2b of this series we went over what some of the research shows and how this runs counter to what most people are told and end up doing to lose weight.  Here’s a recap:

A calorie is indeed a calorie, but your body doesn’t use calories.  A Calorie is a measure of things your body uses, namely carbohydrates, protein and fats.  However, what you eat is not merely energy, it is raw materials for cell membranes, hormones, enzymes and a host of other important chemicals and structures

As you lose weight by lowering calorie intake, your body lowers your metabolism making the calorie you burned when you started much easier to burn than the calorie you burn after dropping 50lbs.  Conventional wisdom is that this is a result of your body protecting body fat stores for times of famine.  However, if you overconsume calories, your body will actually increase metabolism and in both instances it is capable of altering metabolism by 25%.  If your body truly was trying to conserve energy, why would the rules change when you are eating to excess?

Obviously your body adjusts metabolism to the energy intake you provide it with.  This is your body adapting to the environment it is in.  If you provide too much energy, your body increases energy output and when you decrease energy your body lowers energy output.  Looking at it in terms people can understand, which car do you have more faith in, one that can go 500 miles on a tank of gas or 400 miles?  Assuming they are identical, you have to wonder where all of the extra energy is going in the less efficient car since it is not being used for driving further.  In humans, it’s quite possible that the extra energy is speeding up all of your body processes, which is not good.  Efficiency is good, especially when you are dealing with your body, cell division, and repair processes.

While some of your cells will only run on glucose, it is not the preferred fuel for your body.  Your body’s preferred fuel is based on what you put it through via the day, i.e., your environment.  If your job or life is filled with a lot of high force activity, glucose is your body’s preferred fuel.  If you are part of the 99% of people in the United States that sit for hours at a time, drive an hour to work, and only bend over to pick up the piece of donut they dropped, this doesn’t apply to you and fat is your guy.

Mismatching fuel to both what you are engineered to run on (Your genes) and the type of activity you perform drives obesity and diabetes.

Diet is not the only player in this story, exercise is a significant player as well.  When your diet doesn’t match your activity type and level, insulin is used to shuttle glucose in to your muscle and liver cells for storage.  It isn’t that insulin is a bad thing, if you look at Type 1 Diabetics who don’t produce any, you can clearly see how important it is.  The problem with insulin is when we rely on it as the primary way of getting glucose out of our bloodstream and in to our cells.  Once your cells’ glycogen stores are full they stop listening to insulin and you begin to convert the glucose to fat.  High levels of insulin help shuttle this fat in to your fat cells.  Exercise also shuttles glucose in to the cells but instantly burns it.  Provided the intensity of exercise is sufficient, exercise also empties glycogen out of muscle cells and improves their sensitivity to insulin, making it less likely glucose will be turned in to fat and stored.  In the long term, exercise also increases the amount of glucose your body can store as glycogen, allowing a higher consumption of carbohydrate before conversion to fat.

Control of appetite
Now that we have gone over the way our muscles use fuel, we need to direct our attention to appetite.  The primary difference between us and a machine with regard to energy is that we are capable of providing ourselves with energy, and the signal to do this is via appetite.  Appetite is dictated by the interplay between the hypothalamus in the brain, the gastrointestinal tract, and adipose (Fat) tissue.  Both hormones as well as circulating levels of glucose and fatty acids provide information to the hypothalamus so that appetite can be adjusted.  The primary hormones that deal with regulating appetite are Ghrelin, PYY, Leptin, and insulin.
Ghrelin is a hormone secreted by the empty stomach to stimulate food uptake.  Once you eat and the food enters your stomach, ghrelin release is stopped, signaling you to stop eating.  PYY, on the other hand, is released after you eat to signal that you are in a fed state and can stop eating.  Both of these hormones work by controlling the secretion of appetite stimulating Neuropeptide Y and AgRP; ghrelin by increasing secretion and PYY by inhibiting it.  Leptin, on the other hand, is a completely different animal.

When you consume too much food, whether it is from fat or carbohydrate, the excess energy is converted in to fat.  As you starting making triglycerides, the storage form of fat, they move to adipose tissue where they are stored.  This releases the hormone leptin from the adipose tissue, which signals the hypothalamus to decrease appetite.  In the short term, insulin tends to signal the hypothalamus to curb appetite in a similar way.  In the long term, high levels of insulin seem to have the opposite effect, increasing appetite.

Leptin resistance
As your body fat increases, it secretes more leptin to signal a fed state.  While body fat increases you become insulin resistant, and as this body fat continues to secrete leptin, you actually become leptin resistant.  In a healthy individual, the hypothalamus gets the signal that high levels of leptin mean you no longer need to eat, but in the leptin resistant individual, the cells within the hypothalamus either don’t get the signal or ignore it.  Despite having high levels of circulating leptin, obese individuals that are leptin resistant do not get the fed signal and their appetite remains high.  It’s not that they are always hungry, it’s that they never get the signal to stop eating.  As you can see, leptin resistance and insulin resistance run hand in hand with one another.  If you can control insulin resistance you can control leptin resistance, allowing your hypothalamus to properly control appetite.

This is by no means a comprehensive list of hormones within the body that control appetite, but these are the major players.  As mentioned above, circulating levels of glucose and fatty acids also play a major role in the regulation of appetite.  In fact, if you are insulin resistant, the nutrient partitioning (Fuel selection) effects of insulin can boggle this signal and not only inhibit fat loss, it can also make the effects of cutting your caloric intake unbearable.

Trappings of caloric restriction
Anyone who has undertaken a weight loss program by either reducing calories or exercising away the pounds has at one time felt voraciously hungry, irritable, dizzy, brain fog, or just a complete lack of energy.  Eventually you reach a tipping point and go on a food binge, undoing most of the weight loss progress you have accomplished up until that point.  Most of this can be very easily explained when you look at what you eat, not how much.

When most people decide to tackle a weight loss program, they will cut their calories to some number, let’s say 1500, and begin exercising.  For the most part, people will keep their carbohydrates at 50% of their calories which leaves them with 187.5 grams of carbohydrate.  It has been established that when the brain and central nervous system use glucose as their primary fuel, they need approximately 150g for proper functioning.  This leaves 37.5g of glucose for the rest of your body to use.  The problem with this situation is that even just taking resting metabolism in to account, this is not enough.  So, not only are you already starting out in a hole, once you exercise you have depleted some of the glucose that would be later used for the brain. 

A 130lbs woman will burn approximately 60g of glucose during an hour long run at a pace equivalent to a 10 minute mile.  Increasing the intensity you run at not only increases the amount of carbohydrates you burn via an increased calorie burn, it also increases the percentage of carbohydrate you burn, a double whammy.  This energy is taken out of the system as it is performed, so the brain will eventually enter a low energy state unless you provide it with more fuel.  Just taking in to consideration total daily carbohydrate intake and not accounting for the fact that this exercise may have been done while you have only consumed 1 or 2 meals, this leaves you with 127.5g of carbohydrate for a system that needs 150g.  Interestingly enough, this system also contains the appetite center.

Your brain on ketones
As you can see, a single exercise session of an hour can cause your brain to enter a low energy state while carbohydrate is the dominant fuel source, leaving you hungry and negatively impacting brain function.  This doesn’t even take in to account the glucose that is used for other parts of the body that can only run on glucose as well as other physical activity you may take part in.  It is very easy to see how this could leave you feeling hungry, irritable, preoccupied with food, and a little off mentally.  All is not lost, however.  While it was thought for many years that the brain could only run on glucose, there is actually another fuel the brain can use.  The best part about this fuel is that you will not run out of it until you run out of body fat.  This fuel is a byproduct of fatty acid metabolism called ketones.

Most people familiar with the Atkins diet have heard of ketones or ketosis.  Ketones are essentially the leftovers once a fatty acid has been metabolized for energy and can be metabolized for energy by the heart and the brain.  With ketones provided as an energy source, the brain can function on less carbohydrate, allowing the rest of the body to use what it needs without negatively impacting brain function.  As a substitute for glucose, ketones can provide up to 70% of the brain’s energy needs, lowering the amount of glucose necessary for proper function from 150g to 45g.  Provided you have a good amount of fat to lose, the brain will not enter a low energy state until those fat stores are gone, which is more or less the point of a fat loss program.

The question now becomes, “How do we get the brain to run on ketones?”  In a healthy individual who has good insulin sensitivity and who exercises regularly, ketones probably provide some energy for the brain.  In an insulin resistant individual, high levels of insulin prevent ketones from being formed by blocking the release of body fat stores AND inhibiting fat burning.  In addition, having a high level of carbohydrate in the diet while at the same time eating every 3 hours will cause insulin to be secreted for a couple of hours after every time you eat, which brings us to another myth.  Eating every 5 hours is foolish and will not dramatically impact your metabolism.  In fact on a moderate to high carbohydrate diet it will do more harm than good.
The thermic effect of food, the number of calories used to process what you eat, is related to the amount of food you eat, not how many times you eat.  For comparison’s sake, the thermic effect of food only accounts for 10% of the calories you consume.  In someone who eats 2000 calories, that effect is 200 calories per day, so we are probably only dealing with a 50 calorie per day difference between eating 5 times a day instead of 3 times.  However, if you eat 5 times a day and get insulin secretion for 2-3 hours after every time you eat, this will lead to 10-15 hours per day that you cannot access body fat stores or burn fat effectively to make ketones for the brain.  This will certainly affect appetite, talk about putting your eggs in the wrong basket.

Becoming keto-adapted
So, how do we get the body to become keto-adapted?  First, you have to repair insulin sensitivity to lower the amount of insulin coursing through your veins so that ketones can be made.  The most effective way to do this is to reduce the amount of carbohydrate you consume for a few days.  The amount of carbohydrate you should consume is variable from person to person, but a general recommendation is under 50g of carbohydrate for 2 weeks followed by a gradual increase to tolerable levels based on activity level (1).  Once you’ve done this and things start working properly, keeping insulin levels low via carbohydrate restriction and properly programmed exercise will allow ketone bodies to be formed.  In the initial period following this adaptation, your brain is not very efficient at using ketones.  People who have done the Atkins diet are probably familiar with ketosis and measuring ketones in your urine.  If you are dumping a significant amount of ketones out of your body via urine, your brain can’t possibly be using them effectively.  In fact, once your brain does start using them, urinary ketone levels should start to drop.

There is another way to get ketones to the brain without consuming a low carbohydrate diet.  Coconut oil contains medium chain triglycerides(MCTs) which are instantly metabolized for energy.  As a result, ketones are formed and can be used by the brain as energy, which may be the mechanism by which coconut oil suppresses appetite.  However, this effect will probably only work on someone who is fit and has a properly operating metabolism.  In other words, if you are insulin resistant, it probably won’t work.  If you are an athlete with good insulin sensitivity, MCTs may be something you want to look in to. 

The benefit of ketones to the brain may be far greater than the effect on appetite and body composition.  It has been hypothesized that the protective effect calorie restriction has on the brain may be related to the use of ketones as a substrate.  Increases in brain-derived neuroptrophic factor (BDNF) that occur during fasting may be triggered by the ketogenic energy pathway as are multiple other protective factors (2).  BDNF is a potent driver of brain neurogenesis, the ability to form new connections in the brain.  From an evolutionary perspective this would make sense, it is obviously beneficial for brain function to be enhanced when food is scarce, and for the greater part of our evolution fasting wasn’t a choice it was more or less forced upon us.  This is all speculation at this point, there have been no good trials looking directly at ketones and neurogenesis in humans.  The fact that the neuroprotective effects of calorie restriction seem to be mirrored during a ketogenic diet provide some support that it is not merely the reduction in calories that are the primary driver.

Hopefully this 3 part series has given you an idea as to how complex the science of weight loss and nutritional intervention is.  While I agree that calories do matter, looking at calories in vs calories out is far too simple of an algorithm to use for weight loss, which is probably why it rarely works when you take in to account all of the factors, including appetite.  We not only have to take in to consideration energy, we have to look at the type of energy, the type of activity being performed, the machinery doing the activity (Fiber type and cell type), as well as appetite.  Taking a comprehensive approach is far more effective than the generalist approach of using the energy balance equation, especially when we are dealing with tissues and organs that can alter which substrate they use for fuel depending on the fuel you provide.  Improving insulin sensitivity via the appropriate exercise and diet as well as getting the brain to run on ketones puts more tools in your tool box.  Whether or not you are improving insulin sensitivity directly via carbohydrate restriction or via calorie restriction is irrelevant, they both will work and through basically the same mechanisms.  However, given appetite is a major consideration that will be negatively impacted by calorie restriction and positively impacted by carbohydrate restriction, the scales easily tip in favor of carbohydrate restriction.


1.       Volek, JS & Phinney, SD.  The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-Saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable (2011).

2.       Maalouf M., Rho J. M., Mattson M. P. (2009). The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies. Brain Res. Rev. 59, 293–315.