Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Ketones are produced normally by the liver as part of fatty acid metabolism. In normal states these ketones will be completely metabolised so that very few, if any at all, will appear in the urine. If for any reason the body cannot get enough glucose for energy it will switch to using body fats, resulting in an increase in ketone production making them detectable in the blood and urine.
How to test for ketones
The urine test for ketones is performed using test strips available on prescription. Strips dedicated to ketone testing include:
- Mission® Ketone
Testing should be performed according to manufacturers' instructions. The sample should be fresh and uncontaminated. Usually the result will be expressed as negative or positive (graded 1 to 4).
It should be noted that ketonuria is different from ketonaemia (ie presence of ketones in the blood) and often ketonuria does not indicate clinically significant ketonaemia.
Depending on the testing strips used, urine testing for ketones either has an excellent sensitivity with low specificity, or a poor sensitivity with a good specificity. However, this should be viewed in the context of uncertainty of the biochemical level of significant ketosis.
Interpretation of results
Normally only small amounts of ketones are excreted daily in the urine (3-15 mg). High or increased values may be found in:
- Poorly controlled diabetes.
- Diabetic ketoacidosis (DKA).
- Poisoning (eg with isopropanol).
- Ether anaesthesia.
- Some metabolic disorders.
Positive test result but 'no' ketones
- Some medications:
- Levodopa - eg, Sinemet®
- Valproic acid
- Vitamin C
Most urine testing kits detect aceto-acetate, not the predominant ketone beta-hydroxybutyrate. It is possible for the test to be negative with high levels of beta-hydroxybutyrate and then, as ketoacidosis improves and ketone levels fall, the urine test becomes positive (to aceto-acetate).
Special cases of ketonuria
Diabetes mellitus and ketones
Metabolically severe insulin deficiency (relative or absolute) produces hyperglycaemia and ketoacidosis. Insulin lack increases release of fatty acids from adipose stores and reduces the rate of fat synthesis.
Lipolysis is further increased by increased catecholamines, cortisol, growth hormone and glucagon. The free fatty acids are transported to the liver for conversion to ketone bodies, which serve as fuels for muscle and fat.
Excess production of ketone bodies (aceto-acetate and beta-hydroxybutyrate) gives rise to ketoacidosis. Beta-hydroxybutyrate accounts for 75% of ketones.
Urine is tested for ketones as part of monitoring of type 1 diabetes mellitus. Home blood glucose and ketone monitoring can possibly decrease the number of hospital admissions due to diabetic ketoacidosis.
Monitoring of ketones is important in all people with diabetes:
- When the diet is low in carbohydrates, exercise levels are high or a combination of both.
- In pregnant women with diabetes and in gestational diabetes.
- When blood sugars are high (over 15 mmol/L).
- In DKA or with suspected ketoacidosis.
Patients with diabetes who detect high levels of ketones in their urine should seek medical advice.
High-protein/low-carbohydrate methods to lose weight
There are a number of weight loss programmes now available, consisting of high-protein diets with very little or virtually no carbohydrates. The idea behind this is that, once the body realises it does not have carbohydrates for fuel, it will use protein stores initially and then fat reserves to produce energy.
The breakdown of fat leads to ketones in the blood which can lead to ketosis and even ketoacidosis. Ketosis is associated with nonspecific effects, such as nausea, weakness, increased sweating and lethargy. There are case reports being published highlighting the potential dangers of ketogenic diets.
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Further reading & references
- British National Formulary
- Wilson LA; Urinalysis. Nurs Stand. 2005 May 11-17 19(35):51-4.
- Mitchell R, Thomas SD, Langlois NE; How sensitive and specific is urinalysis 'dipstick' testing for detection of hyperglycaemia and ketosis? An audit of findings from coronial autopsies. Pathology. 2013 Oct 45(6):587-90. doi: 10.1097/PAT.0b013e3283650b93.
- Samuelsson U, Ludvigsson J; When should determination of ketonemia be recommended? Diabetes Technol Ther. 2002 4(5):645-50.
- Voulgari C, Tentolouris N; The performance of a glucose-ketone meter in the diagnosis of diabetic ketoacidosis in patients with type 2 diabetes in the emergency room. Diabetes Technol Ther. 2010 Jul 12(7):529-35. doi: 10.1089/dia.2010.0011.
- Chen TY, Smith W, Rosenstock JL, et al; A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18 367(9514):958.
- Coppola G, Verrotti A, Ammendola E, et al; Ketogenic diet for the treatment of catastrophic epileptic encephalopathies in childhood. Eur J Paediatr Neurol. 2009 Jul 24.
- Kossoff EH, Zupec-Kania BA, Rho JM; Ketogenic Diets: An Update for Child Neurologists. J Child Neurol. 2009 Jun 17.
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