This page is a broad summary of:
- How our bodies use and store energy from food
- The cause and short-term effects of ketosis
Given the complexity of the human body, to say that this summary only scratches the surface of the many chemical processes, enzymes, and hormones involved in food metabolism would be a massive understatement. Our goal is simply to lay out the basics for those of you who may be new to nutrition or ketosis, but want to understand the science at a deeper level than “don't eat carbs and your brain will use ketones and you’ll burn fat”.
TL;DR (Too Long; Didn't Read) Summary
Your body uses sugar (glucose) and fat as sources of fuel. When glucose is too low to meet your body’s needs, your hormones stimulate the body to release and burn fat instead, creating ketones as a by-product. Some cells (notably those of the brain) can’t use fat for energy directly, but they can use ketones. By restricting carbohydrates, limiting protein to just enough for your muscles, and eating liberal amounts of fat, you can keep glucose low and fat-burning ketone production high.
Part I: Macronutrient Metabolism 101
First, let’s get some terms and definitions straight:
A Ketogenic, or “Keto” Diet is one that accelerates a normal process called ketogenesis, in which your body converts fat to ketones for use as energy. When ketone levels reach roughly .5 mmol/L (millimoles per liter), you are considered to be in a state of nutritional ketosis.
Metabolism: chemical processes, for our purposes the ones that convert food to energy
Enzyme: A molecule that accelerates a chemical reaction, turning one molecule into another
Macronutrients (macros): categories of food that you use to survive: fat, carbohydrates, and protein
Ketone Bodies (ketones): Molecules created from fatty acids in the liver that can be used by the brain, heart, and muscles for energy.
Also, here’s a tip to help you remember the metabolic process:
glyco=glucose; lipo=fat; genesis=creation; olysis=breakdown; neo=new
Therefore: Lipolysis=fat breakdown; Gluconeogenesis=creation of new glucose
Now, if you want to understand how and why ketones are created, you have to understand how the macronutrients are metabolized. The carbohydrates, fats, and proteins in your diet provide two primary sources of fuel that your cells use for energy: glucose and fatty acids.
Sugars and Fiber: The Fuel from Carbs
The first of these fuels, glucose, is one of three simple sugars (monosaccharides) that comprise all of the sugars and starches we eat, otherwise known as simple and complex carbohydrates. When you eat ANY carbohydrate, whether it’s table sugar, bread, broccoli, or an apple, it is eventually broken down into some combination of glucose, fructose, and galactose. Glucose is usable by all cells to create energy. Galactose is almost entirely converted to glucose, so we’ll leave it out of this discussion. Fructose is another animal entirely, and you’ll see why.
Note that the harmful “added” or “refined” sugar that we all hear about usually refers to sucrose (50/50 glucose to fructose ratio), high-fructose corn syrup (45/55 glucose/fructose), and other sugar combinations that are removed from their natural food form (like fruit juices!).
When you hear the term “blood sugar”, this refers specifically to glucose, since that’s the form that all your cells can use.
Fiber is also considered a carbohydrate, but it either passes through your gut undigested (i.e., insoluble fiber) or is fermented by your gut bacteria (i.e., soluble fiber). Fiber has three main benefits(1):
- slowing down digestion of other nutrients and thus limiting their blood sugar response,
- providing nutrients for your gut and the bacteria that live there
- acting as a pipe cleaner for your colon (which is cool if you’re into being regular).
First It Fills Your Muscles (Glycogen Storage)
You digest complex carbs with an enzyme called amylase, and the resulting glucose and fructose enters your bloodstream, each behaving differently.
Any cell requiring immediate energy can metabolize blood glucose for energy in the form of ATP (the final form of energy used by all cells) in a process called glycolysis. The remaining glucose quickly signals your pancreas to release insulin. Insulin is a “storage” hormone that opens the gates to your cells so that glucose (and other nutrients) can enter.
Glucose also passes through your liver before entering the muscle cells to be converted to glycogen and stored for later. The muscles can carry quite a bit (about 300g / 1200 calories), however once glycogen is stored in these cells, it can't come out and can only be used by the muscles. Some glucose that passes through the liver is converted to Low-Density Lipoprotein (LDL) cholesterol (2).
Fructose is different in that it doesn’t trigger an insulin response and is predominantly metabolized in your liver. There, it’s first converted to glucose to be stored as liver glycogen. Liver glycogen can later be used for any cell, but it can only hold a tiny amount (about 120g / 480 calories).
And the Rest Turns into Fat
After immediate energy demands are met and your muscle glyogen and liver glycogen are at capacity, any additional glucose is converted to fatty acids and then to triglycerides in a process called De Novo Lipogenesis (DNL).
De Novo = Within the Body Lipogenesis = Fat Creation
Fructose may be more easily converted to triglycerides through a different process which doesn’t require insulin (3,4). All cells can perform DNL, however it is mostly done by the fat (adipose) and liver cells. Most of these triglycerides are stored as cute, loveable bodyfat, but when too many are made at once they form deposits.
These deposits are known as visceral fat, which builds around your liver, muscles, and other organs. Visceral fat has a strong association to metabolic syndrome (insulin resistance, diabetes, and other heart disease risk factors) (5, 6, 7).
Using Stored Glucose Energy
When most of your glucose is used up or stored and your blood levels drop too low, another hormone called glucagon is released. Glucagon is a “release” hormone that performs the opposite functions of insulin, so it signals your liver to release glycogen (remember, the glucose that entered your muscles had a one-way ticket) to provide more fuel for the rest of your body. All told, with a full tank of liver glycogen you only have about 1-3 days (depending on activity) worth of glucose available for normal bodily functions.
TL; DR Summary
Carbs are made of simple sugars. Glucose or “blood sugar” is the primary cellular fuel. Insulin is made to store it as glycogen in your muscles or liver. Once energy demands and storage capacity is met, the remaining glucose and fructose is turned into fat.
Carbohydrates (macro) → Glucose & Fructose (fuel) → Glycogen (stored fuel)
Fatty Acids: The Fuel You Get from Fat
Let’s look at your other primary fuel source, fatty acids. The fats and oils you eat are all made of triglycerides. Each triglyceride contains 3 units of fatty acids chains and 1 unit of glycerol.
There are a lot of ways we categorize fatty acids, but for now it’s important to understand that fatty acids can be metabolized by almost any cell with a mitochondria, but they can't make their way to our brain and nerve cells due to a protective layer called the blood brain barrier. Unlike glucose, fatty acids are more than just fuel and energy storage. Their other purpose is to make things: hormones, cell membranes, components of nerves, transport vitamins, protect you from toxins, and of course body fat.
When you eat fat, the triglycerides take a more roundabout route before they can be used for their energy. They make it all the way to your intestines pretty much intact...
Long-chain triglycerides (most of them fit this category) are broken apart into individual fatty acids and monoglycerides (1 fatty acid + 1 glycerol). They are then surrounded by bile, absorbed into your intestine wall, re-assembled and surrounded by proteins. Next, they travel through your lymph system before mixing with your blood and entering the liver. So, when you hear that fat takes longer to digest, this is why.
Medium-chain triglycerides (MCT) are able to absorb directly through your intestines and into your blood. Unlike their longer siblings, they can also cross the blood brain barrier (8). This is why you hear of MCTs or coconut oil (which is mostly MCTs) referred to as “brain fuel”.
Short-chain fatty acids (SCFA) are found in dairy or created from the fermentation of soluble fiber (remember fiber?) and are the main nutrients for your digestive system.
Using and Storing Free Fatty Acids
Like all nutrients, the first stop for triglycerides is your liver. Unlike glucose, triglycerides do not trigger a release of insulin. If insulin is already high (due to high glucose), triglycerides are escorted into your fat cells to be stored.
If blood glucose is low, glucagon and epinephrine (adrenaline) are released, initiating a process called lipolysis where triglycerides are broken down to glycerol and free fatty acids (FFA). The FFAs can then enter any cell (except your brain and nerve cells - remember the blood brain barrier?) to be metabolized for energy. The glycerol is either used for energy as well or recycled to make glucose or new triglycerides.
TL; DR Summary
Fats (triglycerides) take longer to digest and don’t trigger insulin. When glucose and insulin are high, triglycerides get stored, when glucose and insulin are low, triglycerides are broken into free fatty acids and burned.
Fat (macro)→ Free Fatty Acids (fuel)→ Triglycerides (stored fuel)
Part II: The Cause and Effects of Ketosis
The Liver is Where the Magic Happens
When your body is in “fat-burning mode” (meaning low glucose and high free fatty acids levels), fatty acids are converted into Acetyl-coA in a process called beta-oxidation. Acetyl-coA is then used by the cells to create energy in the form of ATP, in a process called the Krebs or citric acid cycle (remember this from high school biology?).
Back in your liver, the moment we’ve all been waiting for…
Excess Acetyl-coA from beta-oxidation is used to create the first ketone, acetoacetate (AcAc). This is known as ketogenesis. Acetoacetate undergoes yet another process, yielding acetone and beta-hydroxybutyrate (BHB)*:
- Acetone is expelled in your urine and breath (giving you a faint “metallic” mouth taste and "keto breath")
- BHB leaves your liver to be utilized as an additional fuel source for needy cells.
* Note: You may hear that BHB isn’t a ketone. It’s a ketone body, but not technically a ketone. This distinction is only relevant from an organic chemistry perspective, so for the sake of brevity, we’ll refer to all the ketone bodies as “ketones”.
Why Ketones Are Necessary for Life
There are many long-term benefits of being in a state of nutritional ketosis. Some of these benefits are backed by solid research, others are less certain, but plausible, but here I’ll show you why you absolutely need ketones to survive...
By now you understand that most of your body’s cells can use glucose or fatty acids as fuel, but the blood brain barrier prevents your central nervous system from accessing most (remember MCTs?) free fatty acids.
This is particularly troublesome for your brain, since that hungry beast accounts for 20% of your total energy needs (400 cal per day) and it can’t access your most abundant energy source. You have glycogen stores, but most of those are stuck in the muscles, leaving about a day’s worth of calories in the liver glycogen for your brain to use and without some other energy source, you would drop dead after a few days of ketogenic dieting or fasting…
Fortunately for us all, BHB can cross the blood brain barrier and be metabolized by your brain and nerve cells. Your heart and muscles also have an affinity for ketones (9). In fact, any cell outside your liver (which lacks the required enzyme) and red blood cells (that lack mitochondria) can use ketones (10).
Ketosis and Keto Flu
Within 4-6 hours of carb restriction, you will likely begin to experience mild symptoms of hypoglycemia (low blood sugar): dizziness, headaches, confusion, hunger, fatigue, etc.
The severity will depend on how heinously carb-heavy your diet has been recently. As blood sugar and insulin fall, fat is mobilized and metabolized, and your liver starts to churn out more ketones. You always produce some ketones, but initially, most of them are taken up by your heart and muscles. Once you reach a ketone blood level of >.5 mmol/L, you are technically “in ketosis” because levels are high enough that they can be used by your brain to replace some glucose (11).
However, you are not out of the woods just yet…
As you burn through glycogen for the first 1-3 days, you will also pee out the water they were stored with, about 3 parts water for every 1 part glycogen, taking electrolytes (potassium, sodium, magnesium, calcium, and others) with it. This can lead to electrolyte deficiencies, causing cramping (often in the calves).
You might also feel sluggish and foggy-headed for the first 7-10 days, as the brain is not yet fully adapted to ketones and is still seeking glucose.
These two issues combined are what’s commonly referred to as “ the keto flu”.
Let's keep in mind that when glucose runs low, your body does not immediately send you into an instant fat burning, ketone-induced bliss. All of the metabolic processes we’ve discussed so far involve several steps and various enzymes, which your body produces more or less of depending on how often they’re needed. These enzymes take time to “up regulate” which involves changes to how your DNA is expressed.
After a week or so, your body will have adapted to fat burning well enough that most side effects are replaced by reduced hunger (12), higher energy (13), better moods and mental performance (14, 15), even mild euphoria (16). Within 2 weeks, you are burning fat as your primary source of energy, and your brain is using ketones for up to 70% of its energy needs (9).
Ketosis is relatively fast and easy, but the real lasting benefits come from fat adaption that can only be brought on by extended or repeated periods of ketosis. Remember these timelines may vary depending on your previous carbohydrate intake.
“Adaptation” is a subjective term. Over the course of months, less noticeable changes continue to occur. The most noticeable benefit is a reduction in the time it takes to return to ketosis after a carb-heavy meal (or weekend-long binge). Also, your muscles improve their ability to utilize fat, conserve protein, and quickly switch between utilizing glucose and fat (17). Full fat adaptation from an athletic standpoint deserves its own discussion, but for elite-level athletes, it can take many months.
TL; DR Summary
Fatty acid metabolized in your liver create energy with ketones as a byproduct. Ketones can be used by your brain and nervous system as a partial replacement for glucose. When restricting carbs, you may have temporary side effects for about a week, but as your body adapts to fat burning, you enjoy higher energy, better mental performance, fat loss and better physical endurance.
Amino Acids: The Building Blocks of Protein
So far, we’ve neglected protein, the third macronutrient. Protein is broken down into amino acids. Like fat, protein is used to make things, and amino acids make a LOT of things, including making hormones, enzymes, collagen and muscle tissue. Amino acids can also be metabolized for energy, although your body much prefers glucose and fatty acids. In the early stages of a fast, there is a possibility that amino acids from muscle tissue will be broken down and burned, but this is only a temporary measure; from a survival perspective, it doesn’t make much sense for your body to burn through muscle tissue (making you more and more helpless) when there is an abundance of fat available.
Glucose: Down, But Not Out
Although ketones can be used by almost all cells, some still require glucose. Your red blood cells, for example, are completely dependent on glucose, and your brain requires glucose for at least 30% of its energy. So, glucose is still critical, but since you have multiple ways to make it within your body, it is not essential to eat.
Amino acids in excess of your body’s needs (about .8 g per lb of bodyweight, depending on lean mass and activity level) are moved to your liver to be combined with the leftover glycerol (from mobilization of fatty acids) to create glucose in a process called gluconeogenesis. On a carb-restricted diet, most of the energy created in the liver through beta-oxidation is used to create glucose through this process.
This process is significant because eating too much protein will raise glucose and insulin levels just as easily as eating carbohydrates, thereby halting fatty acid mobilization, beta-oxidation, and ketone production.
TL; DR Summary
Protein (amino acids) can be used as a fuel source, but the body prefers to preserve them unless you eat more than you need. Since your body always needs some glucose, it uses excess amino acids and glycerol left over from triglycerides to make its own glucose. Eating too many carbohydrates OR protein triggers insulin and stops ketosis.
So that’s it!
Although they all contain energy, each macronutrient is used for different purposes and has a very different effect on your hormones and whether or not you burn or store fat. The byproducts of fat metabolism are ketones, which serve to fuel the heart, muscles and brain, compensating for the lack of glucose in a ketogenic diet. After 1-3 days, you can produce enough ketones to fuel the brain, and your body continues to adapt to fat-burning over the course of weeks and months.
Hopefully, this provides enough knowledge to distinguish the difference between nutrition science and nutrition marketing.