Ketone Levels

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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. Jump up to: 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. Jump up 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. Jump up 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. Jump up 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. Jump up 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. Jump up 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. Jump up to: 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. Jump up 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. Jump up 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. Jump up 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. Jump up 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. Jump up to: 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. Jump up to: 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. Jump up 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