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An important aspect of the [[Ketogenic Diet]] is knowing how high the ketone levels are.  
+
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 give more than a vague idea of your ketone levels. 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 still under development and is not widely available. Currently only blood measurement of BOHB seems to be viable.
{{Skeleton}}
+
=Measuring Acetoacetate (AcAc)=
* There are three types of [[Ketones]] beta-hydroxybutyrate (BOHB), acetone (Ac) and acetoacetate (AcAc).
+
AcAc is typically measured in the urine using a test strip, such as the [http://www.amazon.com/Multistix-10-100-Test-Strips/dp/B004WNSZGC Multistix] or the cheaper [http://www.amazon.com/Phinex-Parameter-Urinalysis-Reagent-Strips/dp/B0099WTWTA 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 [[Health Risks of the Ketogenic Diet| detect Kidney Stones early]].)
* AcAc is measured in the urine
+
* This approach is cheap, with the strips costing around $0.20 each.
** Easy and cheap
+
* Unfortunately, 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<ref name="SmithManini2008"/>.)
** Not accurate (semi-quantative) but image analysis ([[KetoAnalysis]]) helps
+
* 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<ref name="Musa-Veloso-2002"/>. [[File:KetoneAcAcUrine.jpg|none|thumb|300px|The level of AcAc in the urine is not accurately measured using dipsticks.]]
** Urine levels may not reflect blood levels of AcAc
+
* To compound matters further, urine levels do not reflect blood levels of AcAc very well.
*** Kidney function
+
** High level of hydration will dilute urine ketone levels<ref name="Kossoff-2011-2035"/>.
*** Time delay
+
** Kidney function can change the urine levels<ref name="Laffel-1999"/> as the kidney will reabsorb AcAc<ref name="Galvin-1968"/>. 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<ref name="Sapir-1975"/>. Most studies demonstrate no maximum reabsorption rate<ref name="Wildenhoff-1977"/><ref name="Sapir-1975"/>.
** Hydration levels change measured values
+
** There is also a time delay if the blood levels are changing, this will not be reflected in the urine levels immediately<ref name="Laffel-1999"/>.
** False positives (trace level) from pigmented urine  
+
** A study indicated that the level of urine AcAc and blood AcAc vary in a non-linear manner, following the equation "y = 0.3x<sup>0.6</sup> + 0.07" (after correction), but r<sup>2</sup> was only 0.59 <ref name="Musa-Veloso-2002"/>. [[File:KetoneAcAcUrineBlood.jpg|none|thumb|300px|The levels of AcAc in the blood and urine follow a non-linear relationship.]]
** False positives from vitamin C, medication, etc.  
+
* 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<ref name="Gilbert-2000"/>.
** Levels of AcAc can be quite different to BOHB levels
+
[[File:KetonesProgressiveStarvation.jpg|none|thumb|300px|Changes in blood ketone levels during progressive starvation<ref name="Cahill2006"/>.]]
* BOHB is measured in the blood
+
* Finally, false positives can occur for a number of reasons.
** Slightly painful
+
** Pigmented urine<ref name="patient.co.uk"/> (trace level only).
** Expensive
+
** Vitamin C<ref name="sensorhealth.com"/>.
** Accurate
+
** Low urine pH (acidic)<ref name="drsperoni.com"/>.
** Recommend meter and sources.  
+
** Increased urine specific gravity<ref name="drsperoni.com"/><ref name="sensorhealth.com"/>.
* Acetone can be measured in the breath
+
** Phenolphthalein (a laxative used in many preparations under various trade names)<ref name="drsperoni.com"/>.
** Not readily available – experimental
+
** The amino acid L-dopa<ref name="drsperoni.com"/>.
** Unclear what the cost will be
+
** Drugs, including
** Overcomes problem of kidney filtration seen with Urine AcAc measurement
+
*** Drugs Levodopa, Bendopa, Brocadopa, Larodopa (all used to treat Parkinson's disease)<ref name="drsperoni.com"/><ref name="sensorhealth.com"/>.
** Some delay between blood ketone changes
+
*** Glucocorticoids<ref name="sensorhealth.com"/>.
** Levels of Acetone and AcAc can be quite different to BOHB levels
+
** Fever or burns<ref name="Medline"/>.
{{KetoSeeAlso}}
+
=Measuring beta-hydroxybutyrate (BOHB)=
 
+
BOHB is measured in the blood using a small 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 [http://www.amazon.com/Nova-Blood-Glucose-Monitoring-System/dp/B0050Z48IU Nova Max] and the [http://www.amazon.com/Precision-Blood-Glucose-Monitoring-System/dp/B000N64MZA Precision Xtra].
 +
* The [http://www.amazon.com/Nova-Max-Plus-Ketone-Strips/dp/B006TIEUS0 ketone test strips for Nova Max] are cheaper (around $27 for 10 strips), but less accurate and there tend to be a high number of 'bad' test strips.
 +
* The [http://www.amazon.com/Precision-Xtra-Blood-Ketone-Strips/dp/B001EL30TM ketone test strips for the Precision Xtra] are far more expensive (around $58 for 10 strips), but better quality.
 +
* The best option I've found is to order the Precision Xtra strips from Canada for $20 for 10 strips. I've ordered from the [http://www.universaldrugstore.com/medications/ketone Ketone Strips from Universal Drugstore] many times and I've been pleased with their service. It takes a couple of weeks for delivery, and shipping is $7.
 +
* You have to draw a drop of blood for this testing, and I'd recommend the [http://www.amazon.com/dp/B002NPCC1A Owen Mumford Advanced Lancing Device] for $9. It's not much less painful than other lancing devices, but every bit helps. I also use the narrow (33) gauge [http://www.amazon.com/dp/B0000DD8VM BD Ultra-Fine Lancets].
 +
=Measuring Acetone=
 +
Acetone can be measured in the breath, but the devices are currently at an experimental stage and it's not clear what the cost would be. This approach 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.
 +
=See Also=
 +
{{KetoList}}
 
=References=
 
=References=
 
<references>
 
<references>
 +
<ref name="SmithManini2008">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 [http://www.worldcat.org/issn/10696563 10696563], doi [http://dx.doi.org/10.1111/j.1553-2712.2008.00175.x 10.1111/j.1553-2712.2008.00175.x]</ref>
 +
<ref name="Laffel-1999"> 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 [http://www.ncbi.nlm.nih.gov/pubmed/10634967 10634967]</ref>
 +
<ref name="patient.co.uk">Urine Dipstick Analysis, http://www.patient.co.uk/doctor/urine-dipstick-analysis, Accessed on 9 January 2014</ref>
 +
<ref name="drsperoni.com">http://www.drsperoni.com/downloads/articles/Urinalysis_Results_Interpretation.pdf Urinalysis Results Interpretation</ref>
 +
<ref name="Medline">http://www.nlm.nih.gov/medlineplus/ency/article/003585.htm Medline Plus Ketones - urine</ref>
 +
<ref name="sensorhealth.com">http://sensorhealth.com/UrineStripFalsePositive-NegativeCauses.pdf Urine Strip False Positive-Negative Causes</ref>
 +
<ref name="Musa-Veloso-2002"> 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 [http://www.ncbi.nlm.nih.gov/pubmed/12081817 12081817]</ref>
 +
<ref name="Gilbert-2000"> 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 [http://www.ncbi.nlm.nih.gov/pubmed/11198492 11198492]</ref>
 +
<ref name="Galvin-1968"> 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 [http://www.ncbi.nlm.nih.gov/pubmed/5185570 5185570]</ref>
 +
<ref name="Sapir-1975"> DG. Sapir, OE. Owen, Renal conservation of ketone bodies during starvation., Metabolism, volume 24, issue 1, pages 23-33, Jan 1975, PMID [http://www.ncbi.nlm.nih.gov/pubmed/234169 234169]</ref>
 +
<ref name="Wildenhoff-1977">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 [http://www.ncbi.nlm.nih.gov/pubmed/835373 835373]</ref>
 +
<ref name="Cahill2006">George F. Cahill, Fuel Metabolism in Starvation, Annual Review of Nutrition, volume 26, issue 1, 2006, pages 1–22, ISSN [http://www.worldcat.org/issn/0199-9885 0199-9885], doi [http://dx.doi.org/10.1146/annurev.nutr.26.061505.111258 10.1146/annurev.nutr.26.061505.111258]</ref>
 +
<ref name="Kossoff-2011-2035">Eric. Kossoff, [http://www.amazon.com/Ketogenic-Diets-Eric-H-Kossoff/dp/1936303108 Ketogenic diets : treatments for epilepsy and other disorders], date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Kindle Offset 2035</ref>
 
</references>
 
</references>

Revision as of 12:49, 13 January 2014

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 give more than a vague idea of your ketone levels. 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 still under development and is not widely available. Currently only blood measurement of BOHB seems to be viable.

1 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.)

  • This approach is cheap, with the strips costing around $0.20 each.
  • Unfortunately, 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].

2 Measuring beta-hydroxybutyrate (BOHB)

BOHB is measured in the blood using a small 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.

3 Measuring Acetone

Acetone can be measured in the breath, but the devices are currently at an experimental stage and it's not clear what the cost would be. This approach 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.

4 See Also

5 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