Measuring Ketones

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An important aspect of the Ketogenic Diet is knowing how high your ketone levels are. There are three types of Ketones; beta-hydroxybutyrate (BOHB) which is measured in the blood, acetoacetate (AcAc) which is typically measured in the urine, and acetone which is typically measured in the breath. The easiest and cheapest technique is to measure AcAc in the urine using a test strip. However, this approach is too inaccurate to be useful. Measuring BOHB in the blood is now practical at home using a similar technique to measuring blood glucose, but is far more expensive. Measuring Acetone in the breath is emerging. Currently, only blood measurement of BOHB is viable, though urine dipsticks are still required to test for kidney stones.

1 Measuring beta-hydroxybutyrate (BOHB)

BOHB is measured in the blood using a small meter similar to a Blood Glucose Meter. A test strip is placed in the meter and a drop of blood is added. After a few seconds, the meter will indicate the level of Ketones. There are two meters on the market in the US, the Nova Max and the Precision Xtra.

2 Measuring Acetoacetate (AcAc)

AcAc is typically measured in the urine using a test strip, such as the Multistix or the cheaper Phinex Multistix equivalent. These strips check for 10 different things in addition to AcAc, including trace blood, hydration status and urine acidity. (It's important to test for trace blood in your urine if you're on the ketogenic diet to detect Kidney Stones early.) The test strips are cheap, costing around $0.20 each.

3 Measuring Acetone

Acetone can be measured in the breath, which would overcome many of the problems seen with urine AcAc measurement. However, there would still be some delay between changes in the AcAc level and the levels of Acetone, as well as differing levels of AcAc and BOHB. However, the simplicity of this approach and possibly the lower cost could be a huge advantage. The first device I've come across is the Ketonix which is reasonably priced at around $110, but only has a simplistic high/medium/low scale and I've read reports of reproducibility errors (repeated tests giving different values.)

4 My Results

I measured my blood BOHB, urine AcAc (using (KetoAnalysis), and my blood glucose. The charts below show the relationship between the values, with the regression line in blue and the 95% confidence intervals shaded. As you can see, for my readings there is better correlation between blood glucose and blood BOHB than there is to urine AcAc. I tried adjusting for hydration using the Urine Specific Gravity values from the test strips, but this made little difference to the correlation. Multiple regression of blood glucose and urine AcAc to blood BOHB did improve the model to r2=0.73.

My blood BOHB against my urine AcAc levels. r2 is 0.43, p < 0.001.
My blood BOHB against my blood glucose levels. r2 is 0.68, p < 0.001

5 Problems with Measuring Urine Ketones

In the past the only viable method of measuring Ketones was to use a Urine dipstick, but this is too inaccurate to be useful.

  • Urine dipsticks require you to match the color of the test strip against reference patches, so it is not particularly precise. Using image analysis (KetoAnalysis) can help somewhat. (The test strips use a nitroprusside reagent which changes color from pink to maroon. The addition of hydrogen peroxide does not improve the ability of the urine tests to detect BOHB[1].)
  • Worse, there is evidence that the values read from urine dipsticks overestimate the level of ketones in the urine. A study that compared the values from Ketostix with an enzymatic test found the formula "urinary acetoacetate = 0.40(dipstick value) + 0.15" would help correct the overestimation[2].
    The level of AcAc in the urine is not accurately measured using dipsticks.
  • To compound matters further, urine levels do not reflect blood levels of AcAc very well.
    • High level of hydration will dilute urine ketone levels[3].
    • Kidney function can change the urine levels[4] as the kidney will reabsorb AcAc[5]. With starvation ketosis, the kidneys increase the reabsorption over time, with one study showing a progression of AcAc reabsorption from 47 (+/-10) mumoles/min on day 3 to 106 (+/-15) on day 10, 89 (+/-10) on day 17 and 96 (+/-10) on day 24[6]. Most studies demonstrate no maximum reabsorption rate[7][6].
    • There is also a time delay if the blood levels are changing, this will not be reflected in the urine levels immediately[4].
    • A study indicated that the level of urine AcAc and blood AcAc vary in a non-linear manner, following the equation "y = 0.3x0.6 + 0.07" (after correction), but r2 was only 0.59 [2].
      The levels of AcAc in the blood and urine follow a non-linear relationship.
  • Further problems arise because the levels of AcAc can be quite different to BOHB levels, as shown below. A study of children using the Ketogenic Diet for epilepsy showed that when blood BOHB levels are over 2 mmol/l, urine AcAc dipsticks indicate levels of 80-160 mmol/l[8].
Changes in blood ketone levels during progressive starvation[9].
  • Finally, false positives can occur for a number of reasons.
    • Pigmented urine[10] (trace level only).
    • Vitamin C[11].
    • Low urine pH (acidic)[12].
    • Increased urine specific gravity[12][11].
    • Phenolphthalein (a laxative used in many preparations under various trade names)[12].
    • The amino acid L-dopa[12].
    • Drugs, including
      • Drugs Levodopa, Bendopa, Brocadopa, Larodopa (all used to treat Parkinson's disease)[12][11].
      • Glucocorticoids[11].
    • Fever or burns[13].

6 See Also

7 References

  1. Silas W. Smith, Alex F. Manini, Tibor Szekely, Robert S. Hoffman, Bedside Detection of Urine β-Hydroxybutyrate in Diagnosing Metabolic Acidosis, Academic Emergency Medicine, volume 15, issue 8, 2008, pages 751–756, ISSN 10696563, doi 10.1111/j.1553-2712.2008.00175.x
  2. 2.0 2.1 K. Musa-Veloso, SS. Likhodii, SC. Cunnane, Breath acetone is a reliable indicator of ketosis in adults consuming ketogenic meals., Am J Clin Nutr, volume 76, issue 1, pages 65-70, Jul 2002, PMID 12081817
  3. Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2035
  4. 4.0 4.1 L. Laffel, Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes., Diabetes Metab Res Rev, volume 15, issue 6, pages 412-26, PMID 10634967
  5. RD. Galvin, JA. Harris, RE. Johnson, Urinary excretion of beta-hydroxybutyrate and acetoacetate during experimental ketosis., Q J Exp Physiol Cogn Med Sci, volume 53, issue 2, pages 181-93, Apr 1968, PMID 5185570
  6. 6.0 6.1 DG. Sapir, OE. Owen, Renal conservation of ketone bodies during starvation., Metabolism, volume 24, issue 1, pages 23-33, Jan 1975, PMID 234169
  7. KE. Wildenhoff, Tubular reabsorption and urinary excretion of acetoacetate and 3-hydroxybutyrate in normal subjects and juvenile diabetics., Acta Med Scand, volume 201, issue 1-2, pages 63-7, Jan 1977, PMID 835373
  8. DL. Gilbert, PL. Pyzik, JM. Freeman, The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones., J Child Neurol, volume 15, issue 12, pages 787-90, Dec 2000, PMID 11198492
  9. George F. Cahill, Fuel Metabolism in Starvation, Annual Review of Nutrition, volume 26, issue 1, 2006, pages 1–22, ISSN 0199-9885, doi 10.1146/annurev.nutr.26.061505.111258
  10. Urine Dipstick Analysis, http://www.patient.co.uk/doctor/urine-dipstick-analysis, Accessed on 9 January 2014
  11. 11.0 11.1 11.2 11.3 http://sensorhealth.com/UrineStripFalsePositive-NegativeCauses.pdf Urine Strip False Positive-Negative Causes
  12. 12.0 12.1 12.2 12.3 12.4 http://www.drsperoni.com/downloads/articles/Urinalysis_Results_Interpretation.pdf Urinalysis Results Interpretation
  13. http://www.nlm.nih.gov/medlineplus/ency/article/003585.htm Medline Plus Ketones - urine