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).  
+
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. My suspicion is that there is a "Goldilocks range" of ketone levels, with higher values indicating insufficient protein intake. It's possible that 1.0-1.5 mmol/L of blood BOHB might be ideal for athletes in order to prevent impaired performance.
{{Skeleton}}
+
=Relative Levels=
=Levels=
+
[[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"/>.
+
* 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]].
+
* Ketone levels in the general population tend to rise from a low level during exercise, but those on a ketogenic diet will typically see their ketones fall from their normal elevated level during exercise<ref name="Balasse-1989"/>.
 +
=Target Levels=
 +
There are no well-defined targets for Ketone levels at which particular changes occur. The list below is a sampling of the levels I've found used.
 +
* The classic 1983 study by Dr Phinney measured the athletes blood BOHB as 1.28 mmol/L at rest<ref name="Phinney-1983"/>. This makes me wonder if there is a "Goldilocks effect" to ketone levels. Too high may indicate too little protein, and poor glycogen stores, that may impair endurance performance.
 +
* 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"/>. Personally, I'd argue this is too low to be considered ketogenic, as this level is seen in people on a high carbohydrate diet after a night's sleep.
 +
* 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"/>. (It is unclear what research these levels are based on.)
 +
* 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"/>.
 +
* The range of 2 to 7 mmol/L<ref name="Vanitallie-2005"/> or 2 to 5 mmol/L<ref name="Veech-2001"/> has been suggested in some literature as a "therapeutic" range.
 +
* 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"/>.
 +
* A 28 day study of five Parkinson's patients on the Ketogenic Diet had blood BOHB levels averaging 6.6 mmol/L (range 4.8 to 8.9) and showed some signs of improvements, though the study was too small for any conclusions to be drawn <ref name="Vanitallie-2005"/>.
 
=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"/>:
{| class="wikitable"
+
{| class="wikitable" style="margin-left: auto; margin-right: auto; border: none;"
 
! Situation
 
! Situation
 
! Ketone Levels (Blood levels of AcAc + BOHB)
 
! Ketone Levels (Blood levels of AcAc + BOHB)
Line 39: Line 49:
 
| 1-5
 
| 1-5
 
|-
 
|-
| Controlled diabetes
+
| Uncontrolled diabetes
| Up to 25
+
| Up to 25 (dangerous ketoacidosis)
 
|}
 
|}
 
=See Also=
 
=See Also=
Line 46: Line 56:
 
=References=
 
=References=
 
<references>
 
<references>
 +
<ref name="Phinney-1983">SD. Phinney, BR. Bistrian, WJ. Evans, E. Gervino, GL. Blackburn, The human metabolic response to chronic ketosis without caloric restriction: preservation of submaximal exercise capability with reduced carbohydrate oxidation., Metabolism, volume 32, issue 8, pages 769-76, Aug 1983, PMID [http://www.ncbi.nlm.nih.gov/pubmed/6865776 6865776]</ref>
 +
<ref name="Balasse-1989">EO. Balasse, F. Féry, Ketone body production and disposal: effects of fasting, diabetes, and exercise., Diabetes Metab Rev, volume 5, issue 3, pages 247-70, May 1989, PMID [http://www.ncbi.nlm.nih.gov/pubmed/2656155 2656155]</ref>
 +
<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="Vanitallie-2005"> TB. Vanitallie, C. Nonas, A. Di Rocco, K. Boyar, K. Hyams, SB. Heymsfield, Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study., Neurology, volume 64, issue 4, pages 728-30, Feb 2005, doi [http://dx.doi.org/10.1212/01.WNL.0000152046.11390.45 10.1212/01.WNL.0000152046.11390.45], PMID [http://www.ncbi.nlm.nih.gov/pubmed/15728303 15728303]</ref>
 +
<ref name="Veech-2001"> RL. Veech, B. Chance, Y. Kashiwaya, HA. Lardy, GF. Cahill, Ketone bodies, potential therapeutic uses., IUBMB Life, volume 51, issue 4, pages 241-7, Apr 2001, doi [http://dx.doi.org/10.1080/152165401753311780 10.1080/152165401753311780], PMID [http://www.ncbi.nlm.nih.gov/pubmed/11569918 11569918]</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>

Latest revision as of 08:07, 18 June 2017

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. My suspicion is that there is a "Goldilocks range" of ketone levels, with higher values indicating insufficient protein intake. It's possible that 1.0-1.5 mmol/L of blood BOHB might be ideal for athletes in order to prevent impaired performance.

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].
  • Ketone levels in the general population tend to rise from a low level during exercise, but those on a ketogenic diet will typically see their ketones fall from their normal elevated level during exercise[5].

2 Target Levels

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

  • The classic 1983 study by Dr Phinney measured the athletes blood BOHB as 1.28 mmol/L at rest[6]. This makes me wonder if there is a "Goldilocks effect" to ketone levels. Too high may indicate too little protein, and poor glycogen stores, that may impair endurance performance.
  • 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[7]. Personally, I'd argue this is too low to be considered ketogenic, as this level is seen in people on a high carbohydrate diet after a night's sleep.
  • 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"[8]
  • 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"[9], 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[10]. (It is unclear what research these levels are based on.)
  • For epilepsy, the recommendation is for AcAc to be 80-160 mmol/L as measured by urine dipstick[11], though this level is not necessarily sufficient[12].
  • The range of 2 to 7 mmol/L[13] or 2 to 5 mmol/L[14] has been suggested in some literature as a "therapeutic" range.
  • 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[12].
  • A 28 day study of five Parkinson's patients on the Ketogenic Diet had blood BOHB levels averaging 6.6 mmol/L (range 4.8 to 8.9) and showed some signs of improvements, though the study was too small for any conclusions to be drawn [13].

3 Example levels

From "Physiological roles of ketone bodies as substrates and signals in mammalian tissues"[7]:

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
Uncontrolled diabetes Up to 25 (dangerous ketoacidosis)

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. EO. Balasse, F. Féry, Ketone body production and disposal: effects of fasting, diabetes, and exercise., Diabetes Metab Rev, volume 5, issue 3, pages 247-70, May 1989, PMID 2656155
  6. SD. Phinney, BR. Bistrian, WJ. Evans, E. Gervino, GL. Blackburn, The human metabolic response to chronic ketosis without caloric restriction: preservation of submaximal exercise capability with reduced carbohydrate oxidation., Metabolism, volume 32, issue 8, pages 769-76, Aug 1983, PMID 6865776
  7. 7.0 7.1 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 12.0 12.1 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
  13. 13.0 13.1 TB. Vanitallie, C. Nonas, A. Di Rocco, K. Boyar, K. Hyams, SB. Heymsfield, Treatment of Parkinson disease with diet-induced hyperketonemia: a feasibility study., Neurology, volume 64, issue 4, pages 728-30, Feb 2005, doi 10.1212/01.WNL.0000152046.11390.45, PMID 15728303
  14. RL. Veech, B. Chance, Y. Kashiwaya, HA. Lardy, GF. Cahill, Ketone bodies, potential therapeutic uses., IUBMB Life, volume 51, issue 4, pages 241-7, Apr 2001, doi 10.1080/152165401753311780, PMID 11569918