What is Acetoacetate and Why is it Important on Keto?

Updated Jan 31st, 2022 – Written by Craig Clarke

Medical review by Jared Hatchard, R.Ph

Without acetoacetate, we wouldn’t be able to experience the benefits of ketones. In fact, the two other ketone bodies — acetone and beta-hydroxybutyrate (BHB) — are formed from the acetoacetate.

This ketone is a trendsetter, paving the way for our bodies to use a more efficient energy alternative when we restrict carbs and/or calories. However, this isn’t all that acetoacetate and its other ketone counterparts have to offer.

In this article, we will take a closer look at what acetoacetate is and its importance for ketosis and the ketogenic diet. Let’s begin by exploring the role that our featured ketone plays in our bodies.

Acetoacetate — The First Ketone Our Body Produces

Acetoacetate — The First Ketone Our Body Produces

For most of us, the primary source of fuel for the body is glucose. It can be burned so quickly and is so readily available from the food we eat that many of us default to using glucose for energy.

When we digest carbs, they either turn immediately into glucose for the body to use or are stored as glycogen within our muscles, liver, and brain.

However, if the diet is not providing enough carbs, such as when someone is fasting or on a ketogenic diet, the body will rely on two metabolic processes pick up the slack: (1) the cells throughout the body will start using more fat for fuel and (2) the liver will ramp up a process known as ketogenesis.

During ketogenesis, the liver converts fatty acids (and some amino acids) into ketones. More specifically, two acetyl-coas — energy shuttling molecules of energy metabolism — are “joined” to form the first ketone body, acetoacetate.

Once acetoacetate is created, it will have one of three fate: (1) It’ll be sent off to other cells and used as fuel, (2) it’ll be converted into a more energy efficient ketone body called BHB and used as energy throughout the body, or (3) it will spontaneously react to create acetone (which is excreted — typically through the breath — and is not used for energy).

In summary, the three ketones that we produce are acetoacetate, BHB, and acetone. The first two are used as an energy alternative to sugar while acetone is excreted almost immediately. Acetoacetate is the first ketone body produced — and without it, BHB and acetone cannot be formed. Below, you can see a chart comparing the 3 types of ketones that are produced:

Difference between ketone types

Now you know the basic mechanisms behind ketone production, but one question still remains: Why does our body waste precious energy producing ketones, if it can just burn fat?

The Purpose of Ketones: Acetoacetate Prolongs Your Life

Acetoacetate Prolongs Your Life

After digging through the research on ketones (which you can find in this article), one clear purpose of ketogenesis emerges: to create fuel for the brain when sugar is not available.

This is absolutely necessary because almost all of our brain cells cannot use fatty acids for fuel.  The process of fat metabolism is simply too slow to keep up with the brains energy needs (and converting protein to sugar by using gluconeogenesis would cause too much muscle wasting), so evolution came up with a better solution — ketones. These small, water-soluble molecules serve as efficient energy shuttles that almost effortlessly travel through the blood and cross the blood-brain barrier. The same cannot be said for fats (except for some medium chain triglycerides).

Once the ketones are in the brain, they act as a quick energy source (similar to sugar) while also being much more efficient than sugar. As a result, the cells accumulate fewer free radicals and reactive oxygen species, protecting the brain from cell damage and cognitive impairment. This is part of the reason why ketones have been found to improve brain health, even in cognitively impaired adults.

The healthiest way to experience these (and the many other) benefits of using ketones for fuel is by following a ketogenic diet. At first, it will be difficult for the body to adapt, but it will eventually start producing and burning more and more ketones — especially BHB.

Acetoacetate and the Ketogenic Diet

Acetoacetate and the Ketogenic Diet

Although acetoacetate serves as an energy producing ketone body, it isn’t the primary ketone that the liver aims to create. As the demand for ketones increases, acetoacetate simply acts a transitional ketone molecule that paves the way for BHB, the most energy efficient ketone, to be produced.

When you first start the ketogenic diet, however, acetoacetate will be created in much higher quantities. At this time, the liver is not ripe enough with ketone producing enzymes and energy substrates to consistently carry out the final step of ketogenesis — the step that produces BHB.

Instead, the final product of ketogenesis, when you first start restricting carbs, is much more likely to be acetoacetate. This is why many first-time keto dieters will notice an unfamiliar odor coming from their urine (because of acetoacetate excretion) or the smell of nail polish remover or overripe fruit on their breath (because of acetone excretion).

Fortunately, as you continue to restrict carbs, your liver will start producing more BHB and regulating ketone levels more efficiently while your other cells improve their ketone burning abilities. Altogether, this means that you will burn more ketones for fuel without excreting so many of them.

To give you a better idea of how long this will take, here are a couple of findings that will put ketone burning into context:

  • Ketone bodies naturally supply 2–6% of the body’s energy requirements.
  • After a 3-day fast, ketones will typically provide 30–40% of the energy. (Reaching this level of ketone use may take a couple of days longer for keto dieters.)
  • After several weeks of keto dieting, ketone bodies can provide up to 70% of the brain’s energy and up to 50% of the energy used for fueling the body’s tissues.
  • The ultimate goal of ketogenesis (ketone production) is to create BHB. The longer that carbs are restricted, the more BHB we will produce.
  • Being in sustained nutritional ketosis is the best way to burn more BHB for fuel, become keno-adapted, and reap all of the benefits of ketones.

Acetoacetate and Ketosis

Ketosis is one of the primary goals of following a ketogenic diet, and acetoacetate production is the first step to reaching that goal.

Technically, ketosis is achieved when you have blood ketone levels of 0.5 millimoles of BHB per liter (mmol/L). This is considered as “mild ketosis”.

Whether you or in ketosis or not depends mostly on your BHB concentrations — and not acetoacetate levels — because BHB is the most prevalent ketone in the body when you are in ketosis, it can be directly tested by drawing a small amount of blood, and it is the one ketone you want to be producing and using more of.

Acetoacetate and Ketosis

Your blood ketone concentration and your subsequent level of ketosis depends on how many grams of carbs and protein you consumed and how long you have been eating a ketogenic diet. Both carbs and protein consumption can decrease your ketone levels (via stimulating insulin release) — and, once you are eating the right macros, it will take several days for the liver to start pumping out enough BHB for you to technically be in ketosis.

For most people, blood ketone levels will rise above 0.5 mmol/L after eating keto for two days to two weeks. If you are eating what you think is “keto” but you are not in ketosis, then this is technically not a keto diet and macronutrient consumption should be adjusted to stimulate ketone production more effectively. Once you have optimized your keto diet and are in sustained ketosis, you will finally be able to experience the unique benefits of ketosis — benefits that no other diet can consistently provide for you.

Benefits of Ketosis

Benefits of Ketosis

Although the ketogenic diet in itself has a plethora of benefits (that you can read about here), for the purposes of this article let’s focus on what using acetoacetate and BHB does for the body.

Here is a brief overview of the benefits that are directly related to ketosis and ketones:

  • Enhanced cognitive function and mental clarity
  • Improved brain cell health
  • Reduction in pain and inflammation
  • Decreased hunger
  • Increased energy levels and endurance

These are the known effects that ketosis can have throughout the body. Plus, when you sustain ketosis for more extended periods of time (i.e., several months), you will be able to experience all of these benefits to the fullest.

Researchers are still discovering more and more about ketones and what they do to our cells. However, our current base of knowledge on the topic provides us with plenty of evidence supporting the therapeutic benefits of ketosis for a wide range of people with various goals and conditions — all of which you can read more about here.

Testing for Ketosis with Acetoacetate (and the Other Ketones)

Testing for Ketosis with Acetoacetate

Although you can check for several signs of ketosis to see if you are producing ketones, the most accurate way to find out if you are in ketosis is by measuring your ketone levels. One of the simplest and cheapest ways to do this is by measuring acetoacetate excreted through the urine.

Urine testing for ketosis can be done by peeing on a urine strip, which then changes color to indicate ketone levels. These are very affordable and can usually be purchased online or at your local pharmacy.

Urine test strips tend to be most accurate within the first few days of keto dieting. One study found that after 24 hours of following the keto diet, urinary acetoacetate levels showed a moderate correlation with BHB levels. The same relationship was found for testing breath acetone levels as well (another method of tracking ketosis).

Unfortunately, both urine test strips and acetone breath meters tend to become less accurate as the person accumulates more time in ketosis. This is because our bodies become more efficient at using and holding onto acetoacetate (keeping it from being excreted) and turning it into BHB as we continue following the keto diet.

Another issue with using urine test strips is that it is impossible to maintain the variable of how hydrated you are across multiple tests. The more hydrated you are, the more diluted your urine will be, which will result in a lower acetoacetate concentration. Conversely, the less hydrated you are, the higher your acetoacetate levels are likely to be.

To avoid any frustration with breath or urine ketone testing, I recommend using a blood ketone meter that tests BHB levels directly. This is the gold standard of ketone measuring, providing you with a definitive answer to two crucial questions: Am I in ketosis? If so, is it a mild, moderate, or deep level of ketosis?

Keep in mind, however, that the blood testing strips will be expensive if you diligently track your ketone levels. This is why you may want to use urine test strips or an acetone breath meter as soon as you start keto dieting. Although they aren’t 100% accurate measures for what you want to know, you can use your knowledge of ketones and these testing methods to your advantage.

When testing acetoacetate levels in your urine, for example, simply check to see if you have lower ketone levels in your urine over time. If this occurs as you continue to follow the keto diet, then it is likely that ketone production isn’t actually going down. Instead, this indicates that the body is producing more BHB and using acetoacetate more efficiently.

If you would like to know exactly what level of ketosis you are in, however, it is best to use a blood ketone monitor. On the other hand, if you don’t require precision, all you will need to do is use the other testing methods or check for multiple signs of ketosis and stick to your keto diet if you are on the right track.

Is Acetoacetate Safe?

There are many common misconceptions surrounding ketosis and high ketone levels. Many medical professionals are taught that having elevated ketone levels is harmful and should be avoided because it will lead to ketoacidosis.

Ketoacidosis, which is commonly called diabetic ketoacidosis, is a dangerous condition that can occur in those with type 1 and type 2 diabetes who don’t have enough insulin to regulate ketone production, either from not making enough or not injecting enough.

Ketoacidosis can also occur in people who are under extremely stressful and calorie restricted conditions and alcoholics if they’ve been binge-drinking for a prolonged period of time without consuming carbohydrates.

Is Acetoacetate Safe?

For a closer look at this potentially life-threatening condition, read through our guide to ketoacidosis.

Fortunately, ketoacidosis is not the same as the nutritional ketosis that occurs as a result of keto dieting. In contrast to the causes of ketoacidosis, the keto diet provokes ketone production and ketosis in a healthy way that the body can easily keep under control. In fact, the combination of the keto diet and ketosis allow us to improve overall health, lose excess weight, and burn fat while maintaining sustained energy and steady blood sugar levels. Plus, it is safe and effective for long-term dieting (for most people).

Key Takeaways — What You Need to Know About Acetoacetate

There are three main types of ketone bodies that can be detected in the bloodstream during ketosis:

Acetoacetate is the first ketone body that your liver produces. During the first few days of keto dieting (or fasting), you are much more likely to create and excrete more acetoacetate and acetone (a spontaneously formed ketone that is virtually useless). To refresh you on this, you can review the graphic below:

How Ketone Bodies are Formed

After carbohydrates are restricted consistently for several days, the body will excrete less acetoacetate and produce much more of the most energy efficient ketone body: BHB. As a result, most of your cells become ketone burning machines, and you experience the many benefits of ketosis.

To test if you are on the right track, you can use indirect ketosis measurements like acetone breath meters or acetoacetate-detecting urine sticks, but they will become less and less accurate as your body adapts to the keto diet. The more precise ketone tracking method is a blood ketone meter that tracks your blood BHB levels directly.

Whether you decide to use these keto tracking methods or not, it is important to remember that you must follow the ketogenic diet correctly to increase ketone levels and reap all of the benefits of sustained ketosis. To figure out what the right keto diet is for you, I recommend reading through our comprehensive beginner’s guide to the keto diet and using our keto calculator.