Science

What Is Ketosis: Understanding the Science Behind This Natural Process

Published on: August 05, 2019

What Is Ketosis: Understanding the Science Behind This Natural Process

Main Page (Index): Ketosis: The Complete Guide

Next Article: Ketones: Types and Their Role in Human Metabolism

You might assume that ketosis is a fad, but it isn’t. Here’s what it’s about: Ketosis is a natural metabolic process where ketone levels in your body rise. You achieve a ketotic state by following a low-carbohydrate and high-fat diet, exercising or fasting [1].

People who are not in ketosis get their energy from dietary carbohydrates. By entering ketosis, the body now relies on stored fat for fuel. Can you imagine the benefits of being able to burn your own body fat [1]?

Before you can start using ketosis, first, understand how it works. We created this guide to give you a detailed explanation about ketosis. We’re also going to discuss its effects, signs, and types.


definition-of-ketosis

What Is Ketosis?

The term “ketosis” refers to a normal physiologic state that you can go in and out of. As we mentioned earlier, in ketosis, your body taps into fat for fuel. That fat comes from your own fat stores. It can also come from the food you eat (a.k.a. dietary fat) [2].

The liver breaks down fat into ketones or ketone bodies. These ketones are acetoacetate (AcAc), beta-hydroxybutyrate (BHB) and acetone.

From your liver, ketones enter the blood and into your tissues to fuel them. These extrahepatic (meaning, outside the liver) tissues include:

  • Brain
  • Heart
  • Kidney
  • Skeletal muscle

Ketones are especially important for the brain because when glucose is in short supply, it cannot use fat directly [3].

Now, you may be wondering:

How can you tell that you’re in ketosis?

You need to test your blood for the presence of ketones. This is a definitive way to check.

Your ketone levels should be anywhere between 0.5-3.0 mM. Also, remember that your blood ketone levels may vary throughout the day [4].


How ketosis works

It’s not enough to know the definition of ketosis. Did you read this guide because you want to use ketosis to your advantage? If so, you need to gain a basic understanding of its science.

Ready? Now, pay attention.

the-rate-of-ketogenesis-depends-on-your-carbohydrate-consumption

One of the most important things you should know is this:

Your liver keeps on producing ketones. This process is called ketogenesis (keto: ketones, genesis: formation). However, the liver creates ketones only in small amounts in normal situations [5].

The rate of ketogenesis depends on your carbohydrate consumption.

It means that if you eat more carbs, ketone production slows down. If you lessen your carbs, you produce more ketone bodies [5].

Low ketone levels mean that ketones are not being used as your body’s main source of energy. Rather, glucose from your dietary carbohydrate intake is used [5].

Here, we appreciate the body’s ability to switch its metabolic state depending on the available fuel. Now, we’re going to discuss the actual ketosis process:


Well-fed state: carbohydrates are abundant

Typically, we get energy from the food we eat, which happens to be high in carbohydrates. We also consider dietary carbohydrates our main energy source [6].

As you eat carbs, your body breaks them down into glucose. Glucose moves through your bloodstream and into your cells. Glucose enters your cells with the help of insulin [7].

If glucose isn’t used, it is stored inside the cells of your muscles and liver. In its storage form, glucose is called glycogen. Skeletal muscles store about 500 grams of glycogen while the liver stores about 100 grams of glycogen [8].


reduce-your-carbohydrate-intake-to-50-grams-per-day

Low-carbohydrate availability

Imagine this:

You reduce your carbohydrate intake to 50 grams per day or less.

Here’s what happens: Your insulin levels decrease in response to low glucose.  Take note that insulin only increases when glucose is high, since insulin is needed to bring glucose inside the cells of your body.

If you have enough glycogen, your body uses it first until it gets depleted.

As your glycogen stores deplete, your body tries to produce its own glucose. We call this process gluconeogenesis, and it happens in the liver. Your body uses non-carbohydrate substrates such as [9]:

  • Lactic acid
  • Glycerol
  • Amino acids (alanine and glutamine)

If you don’t replenish your glycogen stores by eating more carbs, glucose levels drop further. In this case, gluconeogenesis can no longer sustain your glucose needs.

For your body to keep functioning, it finds another way to produce energy.

Now, it turns to ketogenesis.


Ketone body production

Ketogenesis involves a series of processes. We’re going to explain it, so don’t worry.

Before your body can use its stored fat for fuel, it needs to break down triglycerides. Triglycerides are a major component of your body’s fat stores [10, 11].

Enzymes called lipases break down triglycerides into smaller free fatty acids. These free fatty acids enter the mitochondria of your liver. They do so with the help of carnitine palmitoyltransferase (CPT-1) [12].

Inside the liver, fatty acids are further broken down into acetyl-CoA molecules. These acetyl-CoA molecules are used to form ketones. Again, these ketones are:

  • Acetoacetate (AcAc)
  • Beta-hydroxybutyrate (BHB)
  • Acetone

fatty-acids-are-broken-down-into-molecules-that-forms-ketones

AcAc is the first ketone body your liver produces. AcAc will then be converted into BHB or acetone. AcAc and BHB are your main ketone bodies, and BHB is the most abundant. Acetone is the least abundant [13].

Unlike AcAc and BHB, acetone is useless. It doesn’t provide your body with energy. Simply put, acetone is a byproduct of ketosis.

But because it exits your body through your breath, it can help tell that you’re in ketosis.


Extrahepatic tissues use ketones

AcAc and BHB now circulate in your bloodstream. They will be used by your extrahepatic tissues (brain, kidneys, muscles, and heart) for energy.

But before that, the mitochondria of your cells must break them down. This process is called ketolysis.

Inside the mitochondria, AcAc and BHB are converted back into acetyl-CoA molecules. That way, acetyl-CoA can be used in the Krebs cycle or citric acid cycle. This cycle produces ATP, the energy currency of your cells.

Keep in mind that depleting your stored glycogen promotes ketosis. Replenishing it by taking more carbs will inactivate ketosis.

Bottom line? Your body will do its best to fuel your tissues. Carbohydrates are your main fuel while ketones serve as a back-up fuel.

This takes us to the next question: If ketones act as an alternative fuel source, why would you want them? Keep reading.


is-it-good-to-be-in-ketosis

Is It Good for Your Body to Be in Ketosis?

Ketosis is a normal process in the body, but it’s often misunderstood. With what we’ve learned so far, ketosis is beneficial. During situations where carbohydrate is less available, it ensures that our bodies can still function.

Generally speaking, ketosis benefits most people.

Studies show that ketone bodies make better fuel than carbohydrates. Here’s why [13]:

  • 100 grams of glucose produces 8.7 kg of ATP
  • 100 grams of beta-hydroxybutyrate (BHB) produces 10.5 kg of ATP
  • 100 grams of acetoacetate (AcAc) produces 9.4 kg of ATP

Ketone bodies are the winner.

Research also tells us that carbohydrates are not an essential nutrient. However, we use them as our main source of energy because they’re found in most foods [14].

Also, carbohydrate-rich foods contain vitamins, minerals, and fiber. That explains why people who follow a ketogenic plan need micronutrient supplementation.

Being in ketosis has many advantages. Let’s dive deeper into them.


healthy-eating-yogurt-berries-and-chia-seeds-on-spoon

1. Greater satiety

Do you ever wonder why carbohydrates makes you often hungry? This increased hunger leads to weight gain as you eat more carbs.

Carbohydrates spike your blood glucose. An increase in blood glucose triggers an increase in insulin. Insulin induces hunger and makes you eat more food [15].

Nutritional ketosis has anti-inflammatory properties that improve your satiety. A 2017 study found out that exogenous ketones lower ghrelin and insulin. Ghrelin and insulin are hormones that increase hunger [16, 17].


2. Boosts mitochondria and stops the production of free radicals in the brain

Nutritional ketosis can boost the number of mitochondria in your brain cells.

Mitochondria are vital because they produce ATP, an energy-carrying molecule. They also control synaptic transmission, cognition and brain function [18, 19].

Ketones also stop the production of oxidants or free radicals. They do that by increasing brain glutathione peroxidase activity. Glutathione peroxidase is part of your body’s antioxidant system [18].


3. Blood glucose balance

Ketosis can decrease your blood glucose levels. It is because of this that some people who are at risk for diabetes type 2 or already have it, try ketosis.

When done right and with the help of a physician, ketosis can normalize your blood glucose. At the same time, you avoid hypoglycemia or below-normal blood glucose levels.

Woman-Checking-Glucose-Level-With-Glucometer

Why medical supervision is vital

One may ask: “Do I need medical supervision before trying nutritional ketosis?” Yes, you need continuous medical supervision.

The reason is that some health conditions can put a ketoer at risk of

 the following:

  • Hypoglycemia (low blood glucose)
  • Hypotension (low blood pressure)
  • Electrolyte imbalances

Your doctor may need to adjust your medications and track your response to your keto regimen.


ketosis-meaning

Signs of Ketosis

It’s not enough to follow a ketogenic plan and trust that it’ll work. Of course, you need solid proof that your ketone levels have increased.


Luckily, we can count on some definitive signs and symptoms. If you’re eager to find out, check out the list below.

  • Bad breath or “ketosis” breath
  • Reduced appetite and cravings
  • Rapid weight loss during the first few days or weeks
  • Food sensitivities that manifest as diarrhea
  • Constipation due to a lack of fiber
  • Fatigue and a decrease in performance
  • Loss of motivation
  • Difficulty falling asleep (insomnia)
  • Frequent urination
  • Nausea and headaches
  • Irritability
  • Dry mouth and thirst
  • Flu-like symptoms

Many of the uncomfortable symptoms of ketosis don’t last long. Over time, they fade as your body adapts to using ketones for fuel.

These negative symptoms result from carbohydrate withdrawal.

But don’t worry. When you become keto-adapted, you experience many positive changes. These positive effects include but are not limited to:

  • More stable energy levels
  • Better performance
  • Reduced exercise fatigue

ketosis definition

Types of Ketosis

This may come as a surprise. But yes, there are different types of ketosis. As you may have guessed, not all are beneficial for you.


1. Nutritional or dietary ketosis

Nutritional ketosis results from following a low-carbohydrate, moderate-protein and high-fat diet. We call this diet a “keto diet.”

To achieve nutritional ketosis, you should limit your carbohydrates. That way, your body can use the fat in your food or your stored body fat. In nutritional ketosis, you should see your blood ketone levels rise to 0.5-3.0 mM [20, 4].

Experts consider this type of ketosis safe and harmless. In this case, your body produces ketones only in small amounts. They will not alter your blood pH (the acidity or alkalinity of your blood) [13].


2. Post-exercise ketosis

As the term implies, post-exercise ketosis happens as a result of exercise. But how does exercise induce ketosis?

Exercise allows you to enter ketosis by depleting your glycogen reserves. The longer and more intense the exercise, the sooner glycogen runs out. This may explain why low muscle glycogen levels decrease exercise performance. This is especially true among those who follow a standard high-carb diet.

Vigorous exercise decreases insulin concentration and increases epinephrine. Epinephrine stimulates muscle glycogen breakdown. With this glycogen breakdown, free fatty acids become available for ketogenesis [21, 22].

Exercise can briefly increase your ketone levels to 3-5 mmol/L [23]. Some people who restrict their carbs exercise to enter ketosis faster.


3. Starvation ketosis

Prolonged fasting can lead to ketosis. We call this type of ketosis “starvation ketosis.”

Limiting your carbs and protein for more than 1 week increases ketones. Ketones can reach as high as 5-10 mmol/L [23].

While these concentrations are lower than those in ketoacidosis, starvation ketosis has disadvantages. It can deprive you of essential nutrients, reduce your lean muscle tissue, and cause other dangerous side effects [23].

If you decide to try fasting, speak with a doctor first if you:

  • Are prone to hypoglycemia
  • Have a history or currently have an eating disorder
  • Experience low blood pressure
  • Take medications
  • Are breastfeeding or pregnant

You may have heard that combining ketosis and intermittent fasting is a good idea. It speeds up ketone production and results.

But for starvation ketosis to take effect, you need to fast for more than a week. Dr. Catherine Metzgar, a member of the clinical team at Virta Health, doesn’t recommend this [24].

Also, people who are new to ketosis may find fasting extremely difficult. The reason is that their bodies are still dependent on glucose. You can tolerate fasting better once you become keto-adapted.


4. Alcoholic ketosis

While rare, alcoholic ketosis is considered an emergency. Ketones build up in the blood due to consuming large amounts of alcohol. It is common among malnourished people who drink excessively every day [25].

Study shows that frequent alcohol use depletes protein and carbohydrates. Alcohol prevents the body from absorbing these macronutrients. Not just that, alcoholics tend to eat very few nutrients [26].

Chronic alcohol use and malnourishment deplete liver glycogen stores. It leads to ketosis by:

  • Decreasing insulin
  • Increasing cortisol levels and growth hormone
  • Increasing the availability of free fatty acids for the liver

Although the body enters ketosis, alcoholic ketosis is a complication.


Conclusion

So far, you’ve learned that ketosis is a normal process in the body. And while the body produces ketones every day, it does so at a minimal rate. Ketogenesis also remains idle with increased carbohydrate intake. It takes over when glucose is low and glycogen stores are depleted.

People often enter ketosis by following a keto diet. This method is known as nutritional ketosis. You can also achieve ketosis by exercising in combination with nutritional ketosis. Doing this depletes your glycogen faster. It also transiently increases your ketones to 5 mmol/L.

Starvation ketosis can be tricky for most people, and many experts are against it. Alcoholic ketosis, on the other hand, is a consequence of alcoholism.

We hope that this guide helped you understand ketosis better.

Ready to get started with nutritional ketosis?

Before you jump in, do seek medical advice. A qualified physician will help you maximize the benefits of burning fat for energy in a safe manner.


Takeaways

  • Ketones become your alternative fuel for extrahepatic tissues when glucose is low.
  • Compared to glucose, ketones provide more energy.
  • Beta-hydroxybutyrate (BHB) produces the most energy (10.5 kg of ATP per 100 g of BHB)
  • There are ketosis symptoms to watch out for. But the best way to confirm ketosis is through blood testing.

References:

  1. Dashti HM et al. Long-term effects of a ketogenic diet in obese patients. 2004 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716748/
  2. Charlie Foundation for Ketogenic Therapies. Ketogenic Diet Explained. https://charliefoundation.org/learn-about-ketosis/
  3. Diapedia. Ketone body metabolism. https://www.diapedia.org/metabolism-and-hormones/51040851169/ketone-body-metabolism
  4. Phinney S, Virta Team. How... View all references

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