Caffeine Substantially Increases Plasma Ketones in Healthy Adults

INTRODUCTION: This recent Canadian study reports that the caffeine contained in 1  1/2 to 3 cups of unsweetened coffee is sufficient to increase plasma levels of ketones, including β-hydroxybuterate, for several hours.

A pilot Canadian study conducted at the Université de Sherbrooke in Sherbrooke, Quebec and published in the Canadian Journal of Physiology and Pharmacology on November 25, 2016 evaluated the effect of caffeine on the production of ketones in healthy adults. Researchers were interested in caffeine as a ketogenic agent based on its ability to increase lypolysis (the breaking down of fat for fuel).

Method of the Study

Two different doses of caffeine were administered to 10 healthy adults who had fasted for 12 hours and who then ate a breakfast that containing 85 gm carbohydrate, 9.5 gm fat and 14 gm of protein.

Subjects were either given;

(1) no caffeine

(2) a cup and a half of regular drip coffee

(3) three cups of regular drip coffee

The subjects plasma caffeine levels were measured over the next 4 hours and it was found that those that drank 1  1/2 cups of coffee had~ 2.5 mg caffeine per kilogram of body weight and those that drank 3 cups of coffee had ~ 5.0 mg caffeine per kilogram of body weight.

Plasma caffeine over time

Results – the effect of caffeine on ketone production

Subjects that had 1  1/2 cups of coffee (2.5 mg of caffeine per kilogram)  had 88% higher ketone production than subjects that had no caffeine.

Subjects that drank 3 cups of coffee (5.0 mg caffeine per kilogram of body weight) had 116% higher ketone production over subjects that had no caffeine.

β-hydroxybuterate per hour

Expressed as the amount of β-hydroxybuterate in μmol/L, it is evident that this ketone rises significantly in response to caffeine, and rises in a dose-dependent manner. That is, the more caffeine consumed the more β-hydroxybuterate was produced.

Amount of β-hydroxybuterate produced in response to caffeine dose

Researchers reported that the level of ketones found in the blood after 3 cups of coffee was approximately twice that produced after an overnight fast.

This increase in plasma ketones obtained with these doses of caffeine could, at least in the short term (a few hours) contribute to ~5-6% of brain energy needs.


The increase in free fatty acids as well as β-hydroxybuterate is explained by caffeine blocking phosphodiesterase (PDE), preventing the inactivation of cyclic adenosine monophosphate (cAMP) – with increased caffeine leading to higher levels of cAMP.

Cyclic adenosine monophosphate (cAMP) is a cellular messenger that is involved with transferring hormones such as glucogon, which is the main catabolic hormone of the body and which functions to raise both the concentration of glucose and fat in the bloodstream and has the opposite effect of insulin).

Glucagon needs cAMP in order to pass through the plasma membrane, so as a result cAMP serves to regulate glucose, fats and glycogen.

cAMP activates hormone sensitive lipase, an enzyme which breaks down fat (lypolysis). This increased breaking down of fat, increases free fatty acids (FFAs), which can then be converted in the liver to the ketones acetoacetate and β-hydroxybuterate.

Final Thoughts…

While this is a small study, the data supports that a few cups of regular, unsweetened coffee (without any butter or coconut oil added) increases the amount of ketones produced for several hours.

If you are following a low carb diet and are monitoring your blood or urine ketones, be aware that having coffee can increase the amount of ketones your body is producing.

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Vandenberghe C, St-Pierre V, Courchesne-Loye A, et al, Caffeine intake increases plasma ketones: an acute metabolic study in humans, Canadian Journal of Physiology and Pharmacology, 2017, Vol. 95, No. 4 : pp. 455-458 
Dr. David Perlmutter, MD (

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