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
- As shown above, the ratio of AcAc to BOHB can change dramatically during progressive starvation, with BOHB rising far higher than AcAc. Also, during diabetic ketoacidosis (DKA), the ratio of BOHB:AcAc rises from normal (1:1) to as high as 10:1.
- Urine ketone levels vary with the time of day, often being lower in the morning
- The ratio between AcAc and Acetone appears reasonably constant, and is based on the spontaneous, one way decomposition of AcAc into Acetone.
- 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.
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. 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. 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"
- 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", 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. (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, though this level is not necessarily sufficient.
- The range of 2 to 7 mmol/L or 2 to 5 mmol/L 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.
- 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 .
3 Example levels
From "Physiological roles of ketone bodies as substrates and signals in mammalian tissues":
|Situation||Ketone Levels (Blood levels of AcAc + BOHB)|
|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|
|Uncontrolled diabetes||Up to 25 (dangerous ketoacidosis)|
4 See Also
- The classifications and types of Low Carbohydrate Diet.
- An introduction to the Ketogenic Diet.
- My experiences with ultrarunning on the Ketogenic Diet
- How the Ketogenic Diet can be used for the treatment and management of disease.
- Health Risks of the Ketogenic Diet
- The time frame and changes that occur with Ketoadaptation
- What are Ketones
- How to measure Ketones
- What ketone levels to aim for
- The pros and cons of the Ketogenic Diet for athletes
- The Types of Ketogenic Diet
- My Ketogenic Recipes
- Non-Ketogenic Low Carbohydrate Diets
- 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
- 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
- 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
- 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
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- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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