'this hasn't been seen before'

Ketone esters boost endurance in elite athletes: Study


- Last updated on GMT

'...with the same exercise you're preserving glycogen and producing much less lactic acid...' ©iStock
'...with the same exercise you're preserving glycogen and producing much less lactic acid...' ©iStock

Related tags Metabolism Carbohydrate functional beverage beverage

A ketone ester drink developed by an Oxford University start-up for the US Army has shown benefits to elite endurance athletes by unlocking “greater human metabolic potential.”

Ketone esters, normally made by the liver as a back-up energy source when someone is observing a low-carbohydrate diet or fasting (state of ketosis), were shown to boost athletic performance, with cyclists riding 400m further over 30 minutes compared to control in one of the five study arms. That was a 2% improvement, significant in elite cycling terms.

“We have demonstrated the metabolic effects of elevated circulating ketone bodies as a fuel and biological signal to create a unique physiological condition,”​ the researchers concluded.

“Ketosis may alter substrate competition for respiration, while improving oxidative energy transduction under certain conditions, such as endurance exercise.”

The single-blind, cross-over, randomised trial​ published in Cell Metabolism​ involved 39 injury and illness-free professional or semi-professional, 18-40 year old, British resident mostly male (except two) rowers, cyclists or triathletes.

"The ketone itself is inhibiting glycolysis, so that with the same exercise you're preserving glycogen and producing much less lactic acid - this hasn't been seen before,”​ said researcher, professor Kieran Clarke, professor of physiological biochemistry at Oxford University Department of Physiology, Anatomy & Genetics and CEO of UK ketone-focused start-up, TdeltaS. 

Previous research has been animal-based or remained unpublished.

The researchers suggested the introduction of ketone esters provoked the performance-enhancing physiological shift - altering the "hierarchy of fuel selection"​ - to a state of or like ketosis. Other research has shown the body must be in a state of ketosis for a long period of time - perhaps months - before it would respond to the introduction of ketone esters and switch or moderate glucose and fat use to sourcing ketones for energy.


The ketone ester was produced via trans-esterification of R-1,3-butanediol (R-1,3-hydroxybutyl) and ethyl-β- hydroxybutyrate using enzymatic catalysts in a patented process to produce the raw monoester (D-β-hydroxybutyrate-R 1,3-Butanediol).

In the five arms of the study the participants, some of whom were former Olympians, were given either carbohydrates, fats, vitamin B or ketones in varying combinations.

The athletes performed exercises including 'until-exhaustion' tests, and cycling at different intensities for different periods of time (30, 45, 60 and 120 minutes).

The study group drank formulations varying from 40%-96% ketone esters of total calories before each trial, dosed at 573 mg/kg of athlete body weight.

"Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin,"​ they said.

"Here we show how a nutritional source of ketone bodies alters conventional muscle fuel metabolism and physical performance, alone and in combination with nutritional carbohydrates. This physiological state operates in contrast to that of endogenous ketosis, where replete glucose reserves, an intact insulin axis, and elevated ketone bodies would never usually coexist.

Participants were asked to avoid strenuous exercise 48 hours before each test, with no alcohol and caffeine 24 hours before, and to consume an identical meal the night before testing.


TdeltaS is awaiting EU novel foods approval (necessary for all ingredients not on market before May, 1997) for its corn-sourced ketone esters, but expects a product to be on-market next year, with the US the first port of call where its ketone esters have GRAS (Generally Regarded As Safe) approval from the US Food and Drug Administration (FDA).

Professor Clarke previously​told us “7 to 8 pro cycling teams”​ had contacted her firm over the years to procure ketones but she has refused all requests in lieu of EU novel foods approval. "We have never sold [our ingredient] to any athlete, or team or in a sporting event."

Ketone forms like acetone, acetoacetate, acetophenone and 3-beta-hydroxybutyrate have appeared on-market for 1000s of euros per litre. 

TdeltaS' novel foods application to the UK Food Standards Agency (FSA) for its ketone ester specifies high-performance sports, but it is uncertain when that process is likely to conclude.

Professor Clarke has been working in ketone and ketogenic (low-carb) diet research for about 20 years, much of it focused on health issues like diabetes, Alzheimer’s and Parkinson’s.

The US Defense Advanced Research Projects Agency (DARPA) issued a €9m grant in 2003 which professor Clarke and other researchers benefitted from as it sought to develop energy-efficient foods for its armed forces. UK Sport, the lottery and British government-funded body to develop Olympic and ParaOlympic sports, has also invested in ketones research.

Professor Clarke will speak at a William Reed-UBM-ESSNA (European Specialist Sports Nutrition Alliance) congress the day before Health Ingredients Europe (HIE) on 28 November in Frankfurt, Germany. Click here​ for more on that.


Cell Metabolism

July 2016 (DOI: 10.1016/j.cmet.2016.07.010)

‘Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes’

Authors: Pete J. Cox, Tom Kirk, Tom Ashmore, Kristof Willerton, Rhys Evans, Alan Smith, Andrew J. Murray, Brianna Stubbs, James West, Stewart W. McLure, M. Todd King, Michael S. Dodd, Cameron Holloway, Stefan Neubauer, Scott Drawer, Richard L. Veech, Julian L. Griffin, Kieran Clarke

Related news

Show more

Related products

show more

Nootropics Report 2.0: Brain Health Insights

Nootropics Report 2.0: Brain Health Insights

Content provided by dsm-firmenich | 20-Feb-2024 | Insight Guide

The brain health market is constantly growing and evolving, with more consumers looking for innovative ways to support total mind and body wellness.

Related suppliers


Now on sale in the USA

Posted by Frank,

In case you missed it, Ketone Esters are now on sale in the USA. KetoneAid

Report abuse

Doping practice

Posted by Remo Jutzeler,

Very doubtful that ketones ever become legal supplemental status. First, it has to be taken "in unnatural quantities", which already contradicts the rationale of the WADA definition for doping. Second, "plasma volume increasing techniques" also fall under this definition.

Report abuse

Mind Reductive Stress

Posted by Dr. Michael Helm - Dynamic Nutrition Lab,

beta-HB (an alkohol) is in the reduced state and contributes to reductive stress. Reductive stress leads to non-heme-iron-release, mitochondrial oxygen activation, H2O2-formation, Xanthine Oxidase-increase, NO-increase, and Gucose-oxidation-decrease. The whole situation characterizes the cancer-state. The stuff could turn out to be disastrous.

Report abuse

Follow us


View more