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The Science Behind Keyto, Part One – How The Keyto Breath Sensor Works

Goal

The Keyto is a breath sensor that is designed to help users reliably answer the questions “How much fat am I burning right now?” and “Am I in ketosis?” Keyto does this by detecting the level of a specific biomarker, acetone, in a user’s breath.

Biology

Why measure acetone? 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 adipose (fat) tissue. These fatty acids are produced from enzymes breaking down fat stores at time of need, such as during fasting, starvation or 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 the 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 that humans 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.

2 acetyl-CoA molecules to 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.

The full, basic formula

As Keyto detects acetone, which is expelled through the breath, we can determine the level of fat utilization and level of ketosis for a given user through our breath sensor.

Acetone chemical structure

Keyto Breath Acetone Sensor

 Every Keyto has a proprietary nanostructured gas sensor that is selective to acetone. The sensor consists of a semiconducting metal oxide core, composed of a specific combination of elements that make the sensor selective for acetone. The metal oxide is arranged in nanoparticles sintered together to form a tiny porous bead with extremely high surface area.

The below image shows a planar view of the sensor surface, in progressive zoom, from a scanning electron microscopy:

The production of each sensor requires extensive human and machine processing. Every sensor goes through a complex sequence of assembly, validation, aging, and calibration.

In addition to the metal oxide bead itself, there is a heating element for heating the sensor to over 400 degrees celsius for optimal performance.

How the sensor works

The surfaces of the metal oxide nanoparticles react with oxygen from the air and reducing gases such as acetone, resulting in conductivity changes that can be measured by our readout electronics.

The level of conductivity change produced during a breath measurement is turned into a digital signal. This digital signal is received by a microcontroller, and transmitted to the app via Bluetooth. Through an algorithm derived from machine learning techniques, the the app then converts the digital signal into Keyto Level.

Through extensive research and development and decades of experience with gas sensors, we have found a metal element and oxide combination with remarkable properties. This makes our sensor selectively reactive to acetone (and not other volatile compounds).

Composition of Sensor Scanning Electron Microscopy
Sensitivity of sensor to acetone and other volatile compounds

Testing and calibration

In developing the Keyto*, thousands of lab calibration and human tests were performed. Calibration testing is conducted with known concentrations of acetone gas, which are certified by independent labs. Human testing is done with humans in varying levels of ketosis.

The number of hours spent and the amount of data that has been generated has been immense. In addition to researching the properties of the sensor, a nearly equal effort was spent on developing the mathematical models to translate digital signal into meaningful outputs. These models started off as advanced statistical techniques, but eventually moved into machine learning techniques.

Individual calibration: Each Keyto sensor is individually stabilized and then calibrated with multiple concentrations of standard acetone gas. This process is extremely labor intensive, but we are committed to making sure that every single Keyto delivered is as accurate as possible.

Through this all, we have achieved high repeatability in lab calibration tests, individual tests, and across devices. The ultimate goal is to provide an experience for users that “just works.” To that end, we take pride in making this complex technical process seem simple for users.

*The testing process was led by Ethan J. Weiss M.D. and Ray H. Wu M.D. Dr. Weiss is a world known expert in preventative cardiology and metabolism as an Associate Professor at UCSF and principal investigator at the Cardiovascular Research Institute. Dr. Wu graduated with honors from the Weill Cornell Medical College and has published numerous peer reviewed scientific articles, including in the molecular biology of diabetes and metabolism.

Breath acetone and fat loss

Normal people can have breath acetone of 1 ppm and ketosis is between 2-40ppm.

Breath Acetone Ranges from Review Article1

Numerous studies have been performed2,3,4,5  that study the relationship between breath acetone and fat loss. Virtually all have found that as breath acetone increases, subjects lose weight and fat. While the exact amount of weight loss depends on numerous factors (starting weight, gender, time), multiple studies found that ~2 ppm breath acetone sustained over a week will results in half a pound of body fat burned during that week. These results were achieved in conjunction with a restricted caloric diet.

There is a lack of scientific studies that affect the rate of weight loss as breath acetone levels increase to higher ranges. In addition, high levels may be achieved through other methods such as fasting, exogenous ketone supplements, MCT oils, etc, which result in utilization of varying amounts of body fat and fat from nutritional sources which makes creating specific expectations of weight and fat loss difficult.

At Keyto, we are focused on long term success. Open label clinical trials6,7 have shown that the ketogenic diet can result in long term weight loss, and a recent landmark paper demonstrated that low-carb diets have a positive effect on long term metabolic rate vs low fat diets8.

As part of long term success, we believe that people should not be hungry and thus should not focus on calorie restriction. Rather, people should eat satisfying foods until satiated, which can be done with great results. We have seen this over and over again with users on the Keyto program.

The factors above explain why we chose to create Keyto Levels vs displaying PPMs. PPMs can be confusing, and give a false sense of accuracy as relates to amount of body fat that is being burned (and results to be expected). In contrast, we have optimized the Keyto Level to deliver the information that is most relevant for our users – information that is important in their quest to achieve and maintain nutritional ketosis and lose weight.

Most importantly, Keyto Levels are simple to understand, and provide a reference for each individual user to know their current state of ketosis. This has a near-magical effect on the motivation and enjoyment levels of Keyto users.

Our users have seen an average of 5% body weight lost in the first 5 weeks on Keyto. Many have lost even more. Predictably, the exact amount of weight lost depends on starting BMI, gender, initial diet, and many other individual factors. We look forward to publishing our full data set in a scientific journal in the near future.

Citations

  1. Anderson JC. Measuring breath acetone for monitoring fat loss: Review. Obesity (Silver Spring). 2015;23(12):2327-34.
  2. Kundu SK, Bruzek JA, Nair R, Judilla AM. Breath acetone analyzer: diagnostic tool to monitor dietary fat loss. Clin Chem1993;39:87–92.
  3. Landini BE, Cranley P, McIntyre J. Diet and exercise effects on breath acetone concentration measured using an enzymatic electrochemical sensor. Obesity Society Annual Scientific Meeting. Obestiy Society: New Orleans, LA, 2007, pp 719.
  4. Triffoni‐Melo AT, Dick‐de‐Paula I, Portari GV, Jordao AA, Garcia Chiarello P, Diez‐Garcia RW. Short‐term carbohydrate‐restricted diet for weight loss in severely obese women. Obes Surg2011;21:1194–1202.
  5. Toyooka T, Hiyama S, Yamada Y. A prototype portable breath acetone analyzer for monitoring fat loss. J Breath Res2013;7:036005.
  6. Hallberg, S.J., McKenzie, A.L., Williams, P.T. et al. Effectiveness and Safety of a Novel Care Model for the Management of Type 2 Diabetes at 1 Year: An Open-Label, Non-Randomized, Controlled Study. Diabetes Ther (2018) 9: 583. https://doi.org/10.1007/s13300-018-0373-9
  7. McKenzie AL, Hallberg SJ, Creighton BC, Volk BM, Link TM, Abner MK, Glon RM, McCarter JP, Volek JS, Phinney SD. A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes. JMIR Diabetes 2017;2(1):e5
  8. Ebbeling CB, Feldman HA, Klein GL, et al. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial. BMJ. 2018;363:k4583. Published 2018 Nov 14. doi:10.1136/bmj.k4583