Please note: if your blood glucose level is high, if you are dehydrated, if you are ill, and/or you are feeling unwell, you should always seek immediate medical attention to be evaluated further for the most appropriate diagnosis and treatment.

If you are a person with diabetes, odds are that you’ve heard of ketones and have possibly been warned to check your urine for ketone levels, especially when you are ill or have high blood glucose levels.

What exactly are ketones and are they inherently dangerous? Can people with diabetes have ketones without ill effects? Can people with diabetes safely follow a ketogenic diet?

This article summarizes the evolution of our understanding of ketones and answers the above questions, and more.

What Are Ketones?

So, what exactly are “ketones” or “ketone bodies”? Simply put, these molecules are a byproduct of fat metabolism. Specifically, ketone bodies include the following molecules: beta-hydroxybutyric acid (BHB), acetoacetic acid (AcAc), and acetone. Ketones can offer an alternative physiological energy source when intracellular glucose reserves are low. Various organs can utilize ketones for energy; even the brain, which was long thought to be a solely glucose-dependent organ, can, in fact, run on ketones!

Ketone bodies were first discovered in urine samples collected from people with diabetes in the mid-1800s. Of course, these patients were very ill, as insulin therapy was not yet available. Because they were found in high concentrations in these individuals, ketones were long thought to be abnormal metabolic molecules. However, as more research was conducted, it was recognized that ketones often occur in healthy individuals and that the presence of ketones is often simply indicative of a normal metabolic variant.

Researchers explain that:

“When ketones first came to the attention of physicians in the latter part of the 19th century, it was because they were found in abundance in the urine of patients in diabetic coma. It soon became evident that a vast overproduction of ketones in the body was largely responsible for the devastating clinical manifestations of what is now called diabetic ketoacidosis. Negative views about ketones prevailed… As analytical techniques have gained in precision and sensitivity, ketone bodies have proved to be normal components of blood, not products that appear only when the metabolism of carbohydrate is disordered.”

When are ketones produced as part of a normal physiological state? Simply put, ketones are typically produced during times of fasting or when an individual chooses to consume a very low-carbohydrate diet, such as a ketogenic diet. In fact, most individuals will have some degree of ketosis occurring after a simple overnight (8-12 hr.) fast. Also, certain special circumstances, like pregnancy, can predispose an individual to develop ketones even quicker.

Interestingly, considerable research has even demonstrated the benefits of ketosis (via ketogenic diet) for the treatment of various diseases, especially for neurodegenerative conditions and even certain cancers. You can read more about that here.

Diabetic Ketoacidosis (DKA) vs. Physiological Ketosis

Notably, diabetic ketoacidosis (DKA) is a life-threatening condition that is precipitated by a lack of sufficient insulin. As summarized in our previous learning resource about ketogenic diets:

“DKA is specifically characterized by high blood glucose levels due to a lack of insulin, a very high levels of ketone bodies, and a significantly higher-than-normal anion gap (and thus a dangerous alteration in the blood pH level). Left untreated, DKA is a serious and life-threatening condition.”

This means that DKA can only be diagnosed via specific blood tests that include an analysis of blood pH. The presence of ketones in the blood or urine is not in itself indicative of DKA, but rather suggests ketosis, a normal metabolic state.

Of course, the samples collected from diabetes patients of the mid-19th century that allowed for the identification of ketones were in ketoacidosis, as insulin therapy was not yet available.

In contrast, ketosis, the state of utilizing alternative sources (ketone bodies) for energy when glucose reserves are low, is very different from ketoacidosis. Notably, the concentration of ketones found in the blood is markedly different between the two states.

Researchers explain that after a whole week or so of fasting, healthy individuals will exhibit blood ketone (BHB) levels of ~4-5 mM/L, whereas individuals who present with DKA will often have BHB levels of 20 mM/L and higher. That’s about a four-fold difference and further underscores the important distinction between metabolic ketosis and DKA.

Keep in mind that DKA can only be diagnosed via specific blood tests that include an analysis of blood pH. The presence of ketones in the blood or urine is not in itself indicative of DKA, but rather often suggests ketosis, a normal metabolic state.

Common Misconceptions Explained

Ketones are “unhealthy” : It is possible that you’ve read an oversimplified news article or two about ketogenic diets, or worse, resources that equate ketosis with an unhealthy metabolic state. Rest assured that the available research clearly demonstrates that ketone metabolism is a normal metabolic variant. Moreover, arguments about whether regular fasting or very low-carbohydrate diets are sustainable in the long-term are irrelevant to assessing the safety of ketosis.

: It is possible that you’ve read an oversimplified news article or two about ketogenic diets, or worse, resources that equate ketosis with an unhealthy metabolic state. Rest assured that the available research clearly demonstrates that ketone metabolism is a normal metabolic variant. Moreover, arguments about whether regular fasting or very low-carbohydrate diets are sustainable in the long-term are irrelevant to assessing the safety of ketosis. It’s “dangerous” for people with diabetes to have ketones: As discussed in depth above, there are several parameters (e.g., blood glucose level, specific ketone body concentration, blood pH level) that clearly discern between a benign (and sometimes beneficial) state of ketosis vs. the critical (dangerous) state of ketoacidosis. Also, note that it is understandable why people with diabetes are cautioned about monitoring ketone levels. Hyperglycemia coupled with dehydration (and moreover certain medications; in particular, SGLT-2 inhibitors) can and do result in DKA, which is a very serious, life-threatening medical condition. However, for people with diabetes who have very tight blood glucose control and do not have other risk factors for developing ketoacidosis, the presence of ketones in physiological concentrations is unlikely to be harmful.

Conclusions

In short, ketones are normal metabolic molecules that earlier in history received a bad reputation. Nowadays, we understand that ketosis is a perfectly normal metabolic state, and can even be beneficial in certain circumstances. Not only can we deduce that ketosis likely was an adaptive survival mechanism in times of starvation, but we also understand today that it may benefit certain health conditions.

Moreover, the misconception that “all ketones are bad” or that “ketones are dangerous in people with diabetes” must come to an end, as these notions are simply unsupported by the body of scientific knowledge. This is especially important because very low-carbohydrate diets have been demonstrated to help many people with diabetes optimize their blood glucose control.

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Have you tried a very low carbohydrate diet approach for diabetes management? If so, do you check your ketone levels? What has your healthcare provider recommended? Please share this article and comment with your experiences below.

References

Paoli A, Bosco G, Camporesi EM, Mangar D; “Ketosis, ketogenic diet and food intake control: a complex relationship” (2015) Frontiers in Psychology 6(27): 1-9. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4313585/pdf/fpsyg-06-00027.pdf

Seth P, Kaur H, Kaur M; “Clinical Profile of Diabetic Ketoacidosis: A Prospective Study in a Tertiary Hospital” (2015) Journal of Clinical & Diagnostic Research 9(6): OC01-OC04. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4525534/

VanItallie TB and Nufert TH; “Ketones: Metabolism’s Ugly Duckling” (2003) Nutrition Reviews 61(10): 327-341. https://pdfs.semanticscholar.org/81b4/39c5d6ccd6931e03c41ecafa02b38c3fe79f.pdf?fbclid=IwAR1SQfzSZl8iJ9zUc1jkFLxso66ziLYA9NruqfT6vDBsaVK663TKV2v47tI

Read more about complications, diabetic ketoacidosis (DKA), ketones, low-carb diet, nutritional ketosis.