How Does Ketosis Actually Work?

Welcome to part two of our series on ketosis!

In the first part, we touched on the basics of a high-fat, very low-carbohydrate diet called the ketogenic diet, as well as its potential pros and cons. Now, we want to go a little deeper into what exactly happens in your body when you’re in ketosis.

Keto can be a great way to eat. It lets you enjoy high-fat foods like steak, butter, bacon, and avocado (although you still want to eat plenty of low-carb veggies like cauliflower and kale). With so many delicious food options on the table, keto meal plans tend to be quite satisfying. It's no surprise that keto is rapidly becoming one of the most popular diets around.

But with that excitement can come misinformation. We hope this article helps to explain how your body actually uses fat for fuel and how a ketogenic diet works on a nitty-gritty level. We also hope it helps you navigate the many claims and articles about keto.

By the end of this article, you’ll learn:

• When and how your body gets into ketosis
• Why carbs take you out of keto
• How your cells turn fat into energy (and where it happens)
• How protein affects keto
• How you can mimic ketosis without carb restriction

How does your body get into ketosis?

Ketosis is a metabolic state in which your body breaks down fat into energy. As long as you have some fat in your diet, ketosis is going on all the time – you’re in a mild state of ketosis right now. But if you’re eating carbs, ketosis is pretty minor.

Nutritional ketosis, on the other hand, is when your body stops using carbs as its main source of energy and switches to burning mostly fat for fuel. That’s the goal of a ketogenic diet, because that’s when you start getting the benefits.

You need two things to shift over to nutritional ketosis:

1. 1. Stable, low blood sugar. When you have sugar in your blood (usually after you eat carbs), your body releases insulin. Insulin signals for your cells to start using the sugar in your bloodstream as fuel. It also shuts off fat burning so you can focus on using the sugar first. In other words, insulin turns off ketosis. To get in (and stay in) keto, it’s key to keep your blood sugar low so you don’t produce insulin.
   2. Empty glycogen stores. Your body also stores carbs as glycogen in your muscles and liver. You keep about 400 grams of glycogen squirreled away for times when you need quick energy. Fasting and intense physical activity, for example, use up your glycogen stores.

These two points are why cutting carbs is the central part of a ketogenic diet. When you stop eating carbs:

• Your blood sugar and insulin stay low.
• Your glycogen stores start emptying, with no carbs to fill them back up.

It takes about 48 hours on a very-low-carb diet to deplete your glycogen stores [1]. You may experience short-term side effects like the keto flu, where you feel a drop in your energy levels for a few days. That happens because, without carbs, your metabolism starts a gradual switch to burning fat for fuel. 

How (and where) you turn fat into fuel

Alright. You’ve emptied your glycogen stores and you’re not giving your body any more carbs. It’s looking for sugar and coming up empty. This is when you start burning fat. Your body begins pulling fat from one of two places:

• If you have food in your system, you’ll break down the fat you ate.
• If you don’t have food in your system (say, when you’re sleeping, fasting, or between meals), you’ll use your body fat.

Whether you’re using dietary fat or body fat, the destination is the same: you shuttle fats through your bloodstream and into your liver.

More specifically, you send fats to the mitochondria in your liver cells.

Mitochondria are the power plants of your body – they produce the energy that fuels everything you do. Nearly every cell in your body contains mitochondria. The mitochondria in your liver cells are where the ketogenic magic happens.

There’s a little biochemistry coming here. If you’re not into the details, the big picture is that your liver mitochondria turn fat into ketone bodies, which distribute through your blood for use as energy. If you want a little more detail, here it is:

• When fats reach your liver, your mitochondria break them down through a process called beta-oxidation.
• Fat molecules have long tails; during beta-oxidation, your mitochondria chew up the fat molecule’s tail, piece-by-piece, and spit out acetyl-CoA (we won’t get into the step-by-step biochemistry of beta-oxidation in this article. If you want that, you can find it here).
• Your mitochondria send acetyl-CoA through the Krebs cycle. You may remember the Krebs cycle from a biology class – it’s how your mitochondria turn fats and sugars into ATP, your body’s form of energy.

Let’s summarize that with a simple and poorly aligned diagram. Pardon the crooked arrows.

Acetyl-CoA depends on another compound called oxaloacetate to turn into ATP. If you’re eating carbs, you’ll have a balance of oxaloacetate and acetyl-CoA (illustrated by the scales, below), and your liver mitochondria can turn acetyl-CoA directly into energy.

That’s normally how you turn fat into energy. When you aren’t eating carbs, though, there’s one more step to the process.

Ketone bodies: your main fuel source on a ketogenic diet

Usually, you don’t turn a whole lot of fat into energy, because your mitochondria are mostly focused on burning sugar.

In ketosis, however, you begin shuttling lots of fat into your liver. Your mitochondria burn through it via the process above, which gives them tons of acetyl-CoA.

But without carbs, your liver mitochondria start running out of oxaloacetate. All of a sudden they have lots of extra acetyl-CoA, with no oxaloacetate to help turn it into energy. So your liver mitochondria turn the extra acetyl-CoA into ketone bodies, portable little packages of fuel that they can send to your bloodstream and ship out to other parts of your body. Here are a couple more scales, to illustrate:

On a ketogenic diet, these ketone bodies are your main source of energy. They’re constantly circulating through your blood, waiting for energy-hungry tissues to grab them up. When a cell needs fuel, it pulls ketone bodies from your blood, turns them back into acetyl-CoA, and sends them through the Krebs cycle, where they come out as ATP (energy). Your brain is especially fond of ketones, which may be why many people report increased mental clarity on a keto diet.

To summarize:

• Without carbs, you send extra fat to your liver mitochondria
• Your liver mitochondria turn that fat into acetyl-CoA
• You run low on oxaloacetate without carbs. Without oxaloacetate, you can’t turn all the extra acetyl-CoA into energy
• Instead, your liver mitochondria convert acetyl-CoA into little bundles of fuel called ketones
• Lots of ketones leave your liver, enter your bloodstream, and zoom throughout your body, ready to be used for energy. Here’s another diagram. The ketones are the green dots:

At this point, you’re using mostly fat for fuel. Your tissues are gobbling up ketones for energy. You’ve fully transitioned into a ketogenic state.

How protein affects ketosis

We’ve covered how carbs and fats affect ketosis. But what about protein?

You may have heard that you have to keep protein low on a ketogenic diet, because excessive protein will turn into sugar (a process called gluconeogenesis) and pull you out of ketosis.

This is half true. When you’re eating very low-carb, your body will indeed turn protein into glucose. But it’s expensive to turn protein into sugar. Gluconeogenesis is very inefficient. It uses up a lot of energy and produces a tiny amount of glucose. Your body doesn’t like doing it, and will only make enough glucose from protein to fulfill your basic needs. The rest of the protein it uses elsewhere.

That means you can eat plenty of protein without it turning into sugar. In this study, for example, fasted participants ate 132 grams of protein in one sitting (that’s about a pound and a third of steak). Their blood sugar hardly changed.

The “too much protein = no ketosis” argument isn’t entirely wrong, though. One byproduct of protein metabolism is ammonia, which is toxic (it’s the same stuff in household cleaners). Usually, your liver converts ammonia to urea, which comes out harmlessly in your urine. But if you eat more than about 230 grams of protein a day, your liver gets overwhelmed [2]. At that point, you’ll turn extra protein into glucose, to avoid ammonia poisoning.

Here’s the thing, though: 230 grams of protein is the equivalent of about ten burgers a day. And there are very few compelling reasons to eat ten burgers a day. Most people can maintain or build muscle with far less [3].

One last thought: breaking down protein does create a small amount of oxaloacetate. If you recall from earlier, oxaloacetate has to be low for you to get into ketosis:

So protein can mildly suppress ketosis by increasing oxaloacetate.

Let’s summarize:

• Gluconeogenesis (protein turning into sugar) doesn’t seem to be a big concern for keto
• If you eat 230+ grams of protein a day, you may convert protein to sugar to prevent ammonia poisoning…but that’s way more protein than most of us would ever need
• Protein can suppress ketosis by increasing oxaloacetate. It’s generally a mild effect, though.

We’ll get into exactly how much protein to eat in our next article, which will outline a sample month on a keto diet. In the meantime, just know that protein probably won’t pull you out of ketosis, unless you’re intentionally eating a lot of it.

You can mimic ketosis without carb restriction

There is a way to mimic ketosis without restricting your carbs. The key lies in a special class of fats called medium-chain triglycerides (MCTs). They work a little differently than other fats do.

Let’s say you eat a mashed potato drizzled with olive oil. The sugars from the potato will trigger insulin release while the fat from the olive oil is still circulating through your bloodstream. That insulin release triggers fat storage – your cells will pull the fat from the olive oil out of your bloodstream and hold onto it while you burn through the potato. If you need more energy, you’ll start in on the fat from the olive oil. If you don’t need more energy, you’ll store the olive oil as body fat.

But if you were to drizzle that mashed potato with MCT oil, two things would change:

1. The MCTs metabolize more quickly than other fats
2. They don’t get stored as fat, even in the presence of insulin

MCTs sneak into your portal vein, the pathway that carbs use to get to your liver. That means MCTs metabolize more quickly than other fats. It also means MCTs escape the fat-storing effects of insulin, because they don’t make it into the general circulation of your blood. MCTs go straight to your liver and turn into ketones, even if there are carbs hanging around. You’d burn both the potato and the MCT oil at the same time. For that reason, MCTs never have a chance to store as body fat. In fact, they may modestly increase the number of calories you burn in a day and also make you feel less hungry, much like a full-on ketogenic diet can (although the changes are smaller with MCT oil) [4].

So MCT oil can give you some of the benefits of circulating ketones, even if you don’t cut out all your carbs.

Final thoughts

A ketogenic diet causes a few pretty major changes to your metabolism, and eating keto may offer a few unique benefits. You can read about the upsides and downsides to keto in our first article in this series. Our next one lays out a full guide to eating keto for your first month. Stay tuned, and thanks for reading!