Ketogenic diets—diets that restrict carbohydrates to usually < 50 g/day to induce ketosis—are gaining popularity, for nutritional ketosis has been shown to lead to metabolic advantages including weight management and improvements in glycemic control and blood lipids. However, adhering to such a strict diet to sustain ketosis may be difficult for many. As a result, there has been growing interest in maintaining nutritional ketosis via consumption of exogenous ketone drinks such as ketone esters (KE) and ketone salts (KS).
The commercially available KS are often a mixture of different isoforms (e.g., D- and L-forms) of the ketone body beta-hydroxybutyrate (βHB). Preliminary data suggested that a high amount of KS was required to achieve ketosis, and the metabolic fate of L-βHB was poorly understood. On the other hand, KE can be manufactured as a purer form (D-βHB), and limited data suggested that ingestion of KE rapidly increased blood levels of βHB.
However, there is still insufficient information on what happens to KS or KE once they are ingested by healthy humans. Researchers from the Department of Physiology, Anatomy and Genetics at University of Oxford (United Kingdom) recently conducted a series of metabolic studies to help address this knowledge gap.1
First, the investigators compared effects of acute low (~12 g) and high (~24 g) doses of βHB as KE and KS on ketone body levels in the blood in 15 healthy adult volunteers. They found that KE drinks elevated blood ketone body D-βHB about 50% higher than KS drinks, but L-βHB from the KS drinks was broken down more slowly in the body. The effects of L-βHB in humans warrant further investigations. Both KE and KS decreased plasma free fatty acids, triglycerides, and glucose without inhibiting insulin secretion for 4 hours. KS mildly raised blood and urine pH, whereas KE mildly lowered blood pH temporarily.
Next, the researchers further investigated the property of KE in humans, since it achieved a significantly higher blood ketone body levels than KS. They evaluated the effect of a high-carb, high-calorie meal before a KE drink in 16 healthy volunteers and found that the meal decreased peak βHB concentrations, but subjects remained in ketosis. The effect of KE on free fatty acids, triglycerides, and glucose was not altered by the meal.
Lastly, they administered equal amounts of KE in two methods; 3 separate KE drinks over 9 hours vs. a continuous nasogastric KE infusion for 9 hours. The results showed that although 3 KE drinks led to fluctuations in ketone body concentrations, both methods sustained elevated blood βHB levels and the total D-βHB appearance in the blood was identical.
These short-term data indicate that both KE and KS drinks increase concentrations of blood βHB in healthy humans, with some differential effects in peak βHB concentration, as well as blood and urine pH values. The long-term effects of exogenous KE or KS consumption remain to be investigated.
Why is this Clinically Relevant?
- For individuals on a ketogenic diet, short-term supplementation of exogenous ketone products may help maintain blood concentrations of ketone bodies within the range of nutritional ketosis
- However, long-term effects of exogenous ketone product consumption in humans remain to be investigated
1. Stubbs BJ, Cox PJ, Evans RD, et al. On the metabolism of exogenous ketones in humans. Front Physiol. 2017;8:848.