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Exogenous Ketones

iStock-1443423026As interest grows in ketogenic diets to address a wide range of medical issues far beyond weight loss, research is expanding into the use of exogenous ketones. A recent paper in Experimental Physiology explored the small but growing body of research assessing the therapeutic potential of these interesting compounds across an array of applications.

Once only available to participants in research studies, these products are now commercially available and come in two main forms: beta-hydroxybutyrate complexed with sodium, potassium, and magnesium (ketone salts), or ketone esters. The esters may be more potent, as they typically contain only D-beta-hydroxybutyrate, while most ketone salts are a racemic mix of the D and L forms. (The D form is what is produced by human metabolism and owing to the molecule’s chirality, only the D form can be used for generating ATP.)

It's important to distinguish exogenous ketones from things like MCT oil and coconut oil, which contain medium-chain fatty acids. These fatty acids are more readily converted into ketones in the liver compared to other fats, but they are not actually ketones, themselves. Exogenous ketone salts and esters provide ketones directly and may be more effective for elevating serum ketone levels.

Owing to impaired or reduced glucose uptake or utilization in Alzheimer’s disease and heart failure, exogenous ketones may serve as an alternative fuel for these otherwise energy-deprived organs. The paper explores other potential uses for these compounds, such as modulation of inflammatory pathways, and other papers have studied their use in athletic performance. As promising as these may be in certain circumstances—and this is an exciting new frontier—it’s unlikely that they can mimic all the hormonal and metabolic effects of a ketogenic diet, from which endogenous ketone synthesis (and elevation of serum ketone concentration) is just one of many systemic changes.

In contrast to the all-too common sensationalism and hyperbole employed on social media, the Experimental Physiology paper was measured and cautious:

“Ketone supplements are now commercially available to the general public, being marketed for performance-enhancing properties such as increased mental clarity, enhanced athletic performance, appetite control and others. However, research on the physiological effects of exogenous ketone ingestion – especially repeated consumption over prolonged periods of time – is still in its infancy and claims such as the above are often unsubstantiated, extrapolated, or even in conflict with existing research and the underlying physiology. Although exogenous ketones can serve as a valuable research tool and hold promise in certain settings, it is important to retain nuance and transparency in scientific discourse and general (e.g., advertising, podcast, etc.) discussions.”

 

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