THE HISTORY OF BREATH ACETONE MEASUREMENTS
The history of using breath acetone to determine human ketone levels goes back almost 100 years. Erik Widmark published the first description of methods to measure acetone in alveolar air (the lungs) as well as studies on blood and urine (Widmark 1920b, 1920a, 1919). In this study, the authors successfully demonstrated a method to accurately measure acetone in the breath of patients with diabetic ketoacidosis.An excerpt of Dr. Widmark’s paper on breath acetone from 1920.
In order to understand how we decided to develop a breath acetone sensor as a tool to measure nutritional ketosis as a means to enable weight loss, it is first important to review some basic biology.
Let’s begin with how ketones are made in the liver. The starting material is fatty acids derived from either the diet or mobilized from our from adipose (fat) tissue. These fatty acids are produced from enzymes breaking down fat stores at time of need (fasting, starvation, exercise). The fatty acids are transported by blood to the liver where they are oxidized (burned), and the product of this oxidation is a chemical called acetyl-CoA. Acetyl-CoA is critical source of fuel for our cells and our bodies. It does this by delivering an acetyl group to the citric acid cycle (Krebs cycle) to be used for energy production.
When glucose (sugar) levels are very low, there can be an excess of acetyl-CoA from fatty acids which overwhelms the cellular machinery of the Krebs cycle. This causes shunting of Acetyl-CoA to an alternative pathway, the ketogenesis (ketone production) pathway. When this happens, the liver begins to make ketones. This is an ancient mechanism we evolved to protect us from starvation when food was scarce. Humans can live for months with zero calories from food because we have adapted a mechanism to convert fat stores into energy that our brain, heart, and other tissues can use in the form of ketones.
So how does this happen? The simplest way to think about this is that 2 acetyl-CoA molecules combine and eventually result in formation of a new molecule called acetoacetate.
Acetoacetate is the first of what typically are referred to as ketone bodies. It is broken down by enzymes to two other molecules. The first of these is called β-hydroxybutyrate. It is the “ketone body” measured in most blood tests for ketones. The second is acetone.
Here is the basic formula:
Acetoacetate, β-hydroxybutyrate, and acetone are all commonly referred to as ketone bodies but their performance, physiology, and measurement are very different.
Today, most blood ketone assays (tests) measure β-hydroxybutyrate. Most urine tests measure acetoacetate, and most breath measurements measure acetone. This is because acetone is the only one of the three that is actually small enough to be found in breath.
While acetone measurement in the breath was first described almost 100 years ago, it has not been used widely to detect ketones mostly because it has required expensive equipment and technical expertise. It is also important to note that while there have been many studies comparing the measurement of the three ketone bodies, these have been small studies owing to the technical nature of the acetone measurement.
We have been thinking about how best to measure ketones for a long time. There are certainly advantages and disadvantages to all the methods. But it is important to explain how and why Keyto landed on breath acetone as our primary form of ketone measurement.
The most important thing to consider is the purpose of the measurement. One of the fundamental principles on which Keyto was founded is that rapid feedback in the form of a biomarker can help reinforce positive behavior changes that enhance the success and enjoyment of a weight loss program – in this case, the ketogenic diet. It is important to emphasize the word enjoyment. Personally, having tried every method of ketone measurement thousands of times, I find pricking my finger to get blood not enjoyable and imagine I’m far from the only user with that experience. The same goes for measuring acetoacetate in urine – both of these methods are disruptive. They are also expensive in that they rely on consumable ketone strips that are used once and disposed of. Beyond all that, we also find that blowing into the Keyto breath sensor is relaxing and meditative, rather than painful or disruptive.
Once we settled on breath, that left only one choice in terms of what to measure: Acetone. This was a simple decision as acetone is the only ketone that is detectable in breath.
SO IS MEASUREMENT OF ACETONE USEFUL TO GUIDE WEIGHT LOSS?
Here is the abstract from a 2011 paper showing the effects of short-term carbohydrate restriction on weight loss in obese women. The result was that the carbohydrate-restricted diet led to significant weight loss and fat loss as compared to a control diet. And the only marker that correlated with weight loss were urine and plasma (blood) acetone (de Toledo Triffoni-Melo et al. 2011).
WHAT ABOUT BREATH ACETONE?
Here is an example from the 1960’s showing that measurement of breath acetone can be used to guide weight loss and control, at least in the laboratory setting (Rooth and Östenson 1966).
Below, you can see that breath acetone goes up in obese subjects who go on a calorie-restricted diet and then go even higher on a zero-calorie diet and come right back down after eating. Again, this is early proof of concept that measuring breath acetone can be extremely helpful in guiding weight loss.
Other studies have shown that acetone is an extremely reliable way to detect nutritional ketosis and compares favorably to blood and urine measurement. Here is a list of references: (Ajibola et al. 2013; Blaak et al. 2006; Španěl et al. 2011; Byrne et al. 2000; Qiao et al. 2014; Musa-Veloso, Likhodii, and Cunnane 2002).
And here is a more contemporary review on the use of breath acetone to enable weight loss either through generic calorie restriction, the use of low-carbohydrate high fat diets, or both (Anderson 2015).
Here you can see the relationship between breath acetone and blood beta-hydroxybutryate:
As you can see, there is a very strong relationship between the two analytes using very accurate equipment. And this has led to this summary overview of how breath acetone correlates to different physiological states in humans.
So to summarize:
- There is very good evidence that measuring ketones is useful in weight loss and is particularly useful in guiding those hoping to lose weight on a ketogenic diet.
- The scientific evidence shows that there is no difference in the accuracy or performance (in correlating ketones with fat oxidation or weight loss) of acetone (measured in blood, urine, or breath) or beta-hydroxybutryate (measured in blood) using laboratory-based gold-standard equipment. That is, the science is solid: acetone is at least as good, if not a better biomarker than blood beta-hydroxybutryate.
As we transition from evidence-based literature into the real world utility, the key differentiator will ultimately be the performance of individual sensors. Through extensive research and development, the proprietary Keyto breath sensor has been engineered to be selective for acetone, and each device is individually calibrated for accuracy. We have found that it performs as well or better as all available consumer devices, including the most popular blood ketone meters.
Ultimately, the only outcome that matters is how well a program or tool enables success in a large population. We at Keyto aspired to design a program that enables anyone to achieve and sustain weight loss and better health. We believe that there a many benefits to the ketogenic diet but one that separates it from all others is that it provides a key biomarker to follow to gauge success. And we have found from our own personal experiences as well as from the experiences of our earliest users that using the Keyto breath sensor is enjoyable and extremely effective as a weight loss tool when combined with the Keyto program emphasizing low carbohydrate and healthy fat foods.
The benefits of using breath vs blood or urine ketone measurement is clear. Individuals are able to achieve success with a better overall experience at lower cost and with no hassle. Accurate breath acetone measurement performs extremely well part of a weight loss program, and this is supported by science.
Ajibola, O. A., D. Smith, P. Španěl, and G. A. Ferns. 2013. ‘Effects of dietary nutrients on volatile breath metabolites’, J Nutr Sci, 2.Anderson, Joseph C. 2015. ‘Measuring breath acetone for monitoring fat loss: Review’, Obesity (Silver Spring, Md.), 23: 2327-34.Blaak, E. E., G. Hul, C. Verdich, V. Stich, A. Martinez, and M. Petersen. 2006. ‘Fat oxidation before and after a high fat load in the obese insulin-resistant state’, J Clin Endocrinol Metabol., 91.Byrne, H., K. Tieszen, S. Hollis, T. Dornan, and J. New. 2000. ‘Evaluation of an electrochemical sensor for measuring blood ketones’, Diabetes Care., 23.
de Toledo Triffoni-Melo, Andresa, Ingrid Dick-de-Paula, Guilherme Vannucchi Portari, Alceu Afonso Jordao, Paula Garcia Chiarello, and Rosa Wanda Diez-Garcia. 2011. ‘Short-Term Carbohydrate-Restricted Diet for Weight Loss in Severely Obese Women’, Obesity Surgery, 21: 1194-202.
Musa-Veloso, K., S. S. Likhodii, and S. C. Cunnane. 2002. ‘Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals’, Am J Clin Nutr., 76.
Qiao, Y., Z. Gao, Y. Liu, Y. Cheng, M. Yu, and L. Zhao. 2014. ‘Breath ketone testing: a New biomarker for diagnosis and therapeutic monitoring of diabetic ketosis’, BioMed Res Int, 2014.
Rooth, Gösta, and Stig Östenson. 1966. ‘ACETONE IN ALVEOLAR AIR, AND THE CONTROL OF DIABETES’, The Lancet, 288: 1102-05.
Španěl, P., K. Dryahina, A. Rejšková, T. W. Chippendale, and D. Smith. 2011. ‘Breath acetone concentration; biological variability and the influence of diet’, Physiol Meas., 32.
Widmark, E. M. 1919. ‘Studies in the Acetone Concentration in Blood, Urine, and Alveolar air: I. A Micromethod for the Estimation of Acetone in Blood, based on the Iodoform Method’, The Biochemical journal, 13: 430-45.
———. 1920a. ‘Studies in the Acetone Concentration in Blood, Urine, and Alveolar Air. II: The Passage of Acetone and Aceto-Acetic Acid into the Urine’, The Biochemical journal, 14: 364-78.
———. 1920b. ‘Studies in the Acetone Concentration in Blood, Urine, and Alveolar Air. III: The Elimination of Acetone through the Lungs’, The Biochemical journal, 14: 379-94.