Difference between revisions of "Ketone Levels"

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There are three important [[Ketones]] involved in [[Ketogenic Diet]]s, Acetoacetic acid (AcAc), Acetone, and Beta-hydroxybutyrate (BOHB).  
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There are three important [[Ketones]] involved in [[Ketogenic Diet]]s, Acetoacetic acid (AcAc), Acetone, and Beta-hydroxybutyrate (BOHB). Their levels can vary somewhat independently, and the target levels for different results are not well defined. Blood levels of BOHB from 0.5 to around 3-5.0 mmol/L have been labeled 'nutritional ketosis' and levels over 4.0 mmol/L are probably best for treatment of Epilepsy.
{{Skeleton}}
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=Relative Levels=
=Levels=
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[[File:KetonesProgressiveStarvation.jpg|none|thumb|300px|Changes in blood ketone levels during progressive starvation<ref name="Cahill2006"/>.]]
* Some evidence from treating childhood epilepsy suggests that when blood ketones are over 2 mmol, urine ketones rise to 4+<ref name="Kossoff-2011-2037"/>.
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* As shown above, the ratio of AcAc to BOHB can change dramatically during progressive starvation, with BOHB rising far higher than AcAc<ref name="Cahill2006"/>. Also, during diabetic ketoacidosis (DKA), the ratio of BOHB:AcAc rises from normal (1:1) to as high as 10:1<ref name="Laffel-1999"/>.
 
* Urine ketone levels vary with the time of day, often being lower in the morning<ref name="Kossoff-2011-2274"/>
 
* Urine ketone levels vary with the time of day, often being lower in the morning<ref name="Kossoff-2011-2274"/>
* The ratio between AcAc and Acetone appears reasonably constant, and is based on the spontaneous, one way decomposition of AcAc into Acetone.  
+
* The ratio between AcAc and Acetone appears reasonably constant, and is based on the spontaneous, one way decomposition of AcAc into Acetone<ref name="HayBond1967"/>.
* The ratio of AcAc to BOHB is rather more varied and may change with [[Ketoadaptation]].
+
=Target Levels=
 +
There are no well-defined ketone levels at which particular changes occur. The list below is a sampling of the levels I've found used.  
 +
* The level required to be ketogenic (hyperketonemia) has been suggested as 0.2 mmol/L measured as the combination of AcAc and BOHB in whole blood as this is slightly above the levels seen in "normal" individuals<ref name="Robinson-1980"/>.
 +
* The book "The Art and Science of Low Carbohydrate Living" calls the range 0.5 to 5.0 mmol/L of blood ketones "nutritional ketosis"<ref name="Phinney-2011-p31"/>
 +
* The follow on book "The Art and Science of Low Carbohydrate Performance" suggests that BOHB levels of 0.5 mmol/L to 3.0 mmol/L is "optimal"<ref name="Phinney-2012-p155"/>, with benefits starting at 0.5 mmol/L and improving to 3.0 mmol/L, but levels above 3.0 mmol/L not producing additional benefits<ref name="Phinney-2012-p157"/>.
 +
* For epilepsy, the recommendation is for AcAc to be 80-160 mmol/L as measured by urine dipstick<ref name="Kossoff-2011-p201"/>, though this level is not necessarily sufficient<ref name="Gilbert-2000"/>.
 +
* A study of 74 children on the ketogenic diet for epilepsy found that blood BOHB levels of greater than 4 mmol/L were correlated with better seizure control than those with lower levels<ref name="Gilbert-2000"/>.
 
=Example levels=
 
=Example levels=
 
From "Physiological roles of ketone bodies as substrates and signals in mammalian tissues"<ref name="Robinson-1980"/>:
 
From "Physiological roles of ketone bodies as substrates and signals in mammalian tissues"<ref name="Robinson-1980"/>:
Line 46: Line 52:
 
=References=
 
=References=
 
<references>
 
<references>
 +
<ref name="HayBond1967">RW Hay, MA Bond, Kinetics of the Decarboxylation of Acetoacetic acid, Australian Journal of Chemistry, volume 20, issue 9, 1967, pages 1823, ISSN [http://www.worldcat.org/issn/0004-9425 0004-9425], doi [http://dx.doi.org/10.1071/CH9671823 10.1071/CH9671823]</ref>
 
<ref name="Robinson-1980"> AM. Robinson, DH. Williamson, Physiological roles of ketone bodies as substrates and signals in mammalian tissues., Physiol Rev, volume 60, issue 1, pages 143-87, Jan 1980, PMID [http://www.ncbi.nlm.nih.gov/pubmed/6986618 6986618]</ref>
 
<ref name="Robinson-1980"> AM. Robinson, DH. Williamson, Physiological roles of ketone bodies as substrates and signals in mammalian tissues., Physiol Rev, volume 60, issue 1, pages 143-87, Jan 1980, PMID [http://www.ncbi.nlm.nih.gov/pubmed/6986618 6986618]</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="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="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="Robinson-1980"> AM. Robinson, DH. Williamson, Physiological roles of ketone bodies as substrates and signals in mammalian tissues., Physiol Rev, volume 60, issue 1, pages 143-87, Jan 1980, PMID [http://www.ncbi.nlm.nih.gov/pubmed/6986618 6986618]</ref>
 +
<ref name="Kossoff-2011-p201">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, Page 201</ref>
 
<ref name="Kossoff-2011-2274">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 2274</ref>
 
<ref name="Kossoff-2011-2274">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 2274</ref>
<ref name="Kossoff-2011-2037">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 2037</ref>
+
<ref name="Phinney-2011-p31">Phd Stephen D. Phinney MD, Rd Jeff S. Volek Phd, [http://www.amazon.com/The-Art-Science-Carbohydrate-Living/dp/0983490708 The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable], 2011, publisher Beyond Obesity LLC, isbn 978-0-9834907-0-8, Page 31</ref>
 +
<ref name="Phinney-2012-p157">Jeff Volek, Stephen D. Phinney, [http://www.amazon.com/The-Art-Science-Carbohydrate-Performance/dp/0983490716 The Art and Science of Low Carbohydrate Performance: A Revolutionary Program to Extend Your Physical and Mental Performance Envelope], 2012, publisher Beyond Obesity, isbn 978-0-9834907-1-5, Page 157</ref>
 +
<ref name="Phinney-2012-p155">Jeff Volek, Stephen D. Phinney, [http://www.amazon.com/The-Art-Science-Carbohydrate-Performance/dp/0983490716 The Art and Science of Low Carbohydrate Performance: A Revolutionary Program to Extend Your Physical and Mental Performance Envelope], 2012, publisher Beyond Obesity, isbn 978-0-9834907-1-5, Page 155</ref>
 
</references>
 
</references>

Revision as of 12:40, 13 January 2014

There are three important Ketones involved in Ketogenic Diets, Acetoacetic acid (AcAc), Acetone, and Beta-hydroxybutyrate (BOHB). Their levels can vary somewhat independently, and the target levels for different results are not well defined. Blood levels of BOHB from 0.5 to around 3-5.0 mmol/L have been labeled 'nutritional ketosis' and levels over 4.0 mmol/L are probably best for treatment of Epilepsy.

1 Relative Levels

Changes in blood ketone levels during progressive starvation[1].
  • As shown above, the ratio of AcAc to BOHB can change dramatically during progressive starvation, with BOHB rising far higher than AcAc[1]. Also, during diabetic ketoacidosis (DKA), the ratio of BOHB:AcAc rises from normal (1:1) to as high as 10:1[2].
  • Urine ketone levels vary with the time of day, often being lower in the morning[3]
  • The ratio between AcAc and Acetone appears reasonably constant, and is based on the spontaneous, one way decomposition of AcAc into Acetone[4].

2 Target Levels

There are no well-defined ketone levels at which particular changes occur. The list below is a sampling of the levels I've found used.

  • The level required to be ketogenic (hyperketonemia) has been suggested as 0.2 mmol/L measured as the combination of AcAc and BOHB in whole blood as this is slightly above the levels seen in "normal" individuals[5].
  • The book "The Art and Science of Low Carbohydrate Living" calls the range 0.5 to 5.0 mmol/L of blood ketones "nutritional ketosis"[6]
  • The follow on book "The Art and Science of Low Carbohydrate Performance" suggests that BOHB levels of 0.5 mmol/L to 3.0 mmol/L is "optimal"[7], with benefits starting at 0.5 mmol/L and improving to 3.0 mmol/L, but levels above 3.0 mmol/L not producing additional benefits[8].
  • For epilepsy, the recommendation is for AcAc to be 80-160 mmol/L as measured by urine dipstick[9], though this level is not necessarily sufficient[10].
  • A study of 74 children on the ketogenic diet for epilepsy found that blood BOHB levels of greater than 4 mmol/L were correlated with better seizure control than those with lower levels[10].

3 Example levels

From "Physiological roles of ketone bodies as substrates and signals in mammalian tissues"[5]:

Situation Ketone Levels (Blood levels of AcAc + BOHB)
Fed ~0.1
Fasted 12-24 Hours Up to 0.3
Fasted 48-72 Hours 2-3
Fasted 5-6 weeks (plateau) ~8
Post exercise Up to 2
Late Pregnancy Up to 1
Late Pregnancy, fasted 48 hours 4-6
Neonatal 0.5-1.0
Hypoglycemia 1-5
Controlled diabetes Up to 25

4 See Also

5 References

  1. 1.0 1.1 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
  2. 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
  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 2274
  4. RW Hay, MA Bond, Kinetics of the Decarboxylation of Acetoacetic acid, Australian Journal of Chemistry, volume 20, issue 9, 1967, pages 1823, ISSN 0004-9425, doi 10.1071/CH9671823
  5. 5.0 5.1 AM. Robinson, DH. Williamson, Physiological roles of ketone bodies as substrates and signals in mammalian tissues., Physiol Rev, volume 60, issue 1, pages 143-87, Jan 1980, PMID 6986618
  6. Phd Stephen D. Phinney MD, Rd Jeff S. Volek Phd, The Art and Science of Low Carbohydrate Living: An Expert Guide to Making the Life-saving Benefits of Carbohydrate Restriction Sustainable and Enjoyable, 2011, publisher Beyond Obesity LLC, isbn 978-0-9834907-0-8, Page 31
  7. Jeff Volek, Stephen D. Phinney, The Art and Science of Low Carbohydrate Performance: A Revolutionary Program to Extend Your Physical and Mental Performance Envelope, 2012, publisher Beyond Obesity, isbn 978-0-9834907-1-5, Page 155
  8. Jeff Volek, Stephen D. Phinney, The Art and Science of Low Carbohydrate Performance: A Revolutionary Program to Extend Your Physical and Mental Performance Envelope, 2012, publisher Beyond Obesity, isbn 978-0-9834907-1-5, Page 157
  9. Eric. Kossoff, Ketogenic diets : treatments for epilepsy and other disorders, date 2011, publisher Demos Health, location New York, isbn 1-936303-10-8, Page 201
  10. 10.0 10.1 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