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There are three important [[Ketones]] involved in [[Ketogenic Diet]]s, Acetoacetic acid (AcAc), Acetone, and Beta-hydroxybutyrate (BOHB). {{Skeleton}}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.=Relative Levels=[[File:KetonesProgressiveStarvation.jpg|none|thumb|300px|Changes in blood ketone levels during progressive starvation<ref name="Cahill2006"/>.]]* Some evidence 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 treating childhood epilepsy suggests that when blood ketones are over 2 mmol, urine ketones rise normal (1:1) to 4+as high as 10:1<ref name="Kossoff-2011Laffel-20371999"/>.
* 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<ref name="HayBond1967"/>. * 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 ratio 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 rather more varied "optimal"<ref name="Phinney-2012-p155"/>, with benefits starting at 0.5 mmol/L and may change 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 [[Ketoadaptation]]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=
From "Physiological roles of ketone bodies as substrates and signals in mammalian tissues"<ref name="Robinson-1980"/>:
{| class="wikitable" style="margin-left: auto; margin-right: auto; border: none;"
! Situation
! Ketone Levels (Blood levels of AcAc + BOHB)
| 1-5
|-
| Controlled Uncontrolled diabetes| Up to 25(dangerous ketoacidosis)
|}
=See Also=
=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="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="KossoffPhinney-2011-2037p31">EricPhd Stephen D. KossoffPhinney MD, Rd Jeff S. Volek Phd, [http://www.amazon.com/KetogenicThe-DietsArt-EricScience-HCarbohydrate-KossoffLiving/dp/1936303108 Ketogenic diets 0983490708 The Art and Science of Low Carbohydrate Living: treatments for epilepsy An Expert Guide to Making the Life-saving Benefits of Carbohydrate Restriction Sustainable and other disordersEnjoyable], date 2011, publisher Demos HealthBeyond 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], location New York2012, publisher Beyond Obesity, isbn 978-0-9834907-1-9363035, Page 157</ref><ref name="Phinney-102012-8p155">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, Kindle Offset 2037Page 155</ref>
</references>
