The Skinny on Exogenous Ketones

The potential benefits of a therapeutic ketogenic diet are fascinating. Ketones produced by dietary restriction have been found to enhance cellular energy, reduce oxidative stress, decrease inflammatory processes, and regulate functions of ion channels and neurotransmitters. More info on the effects can be found here.

Yet the idea of consuming at least 80% of your daily calories from fat seems unappealing. Indeed, many struggle to be compliant with this diet plan, myself included. There’s also potential side effects that may turn people off the diet. So is there a work around? How can one reap the benefits of therapeutic ketosis without such a restrictive diet?

Supplemental ketones, or exogenous ketones, are of great interest in this regard. Could they have the same physiological effects of a restrictive ketogenic diet? Can one supplement ketones and eat normally? But do they really work in the same way?

It’s All About the β-Hydroxybutyrate

Exogenous ketones can be in various forms. Ketone salts, ketone esters, medium chain triglycerides (MCTs), or a combination of all three are currently available on the market. The goal of exogenous ketone products is to increase blood levels of the ketone β-hydroxybutyrate (BHB).

These supplements generate a quick and sustained increase in blood ketones that has direct and indirect effects. Some examples include effects on mitochondria, glycolysis (the cellular breakdown of glucose), neurotransmitter levels, receptors for fats, and pathways involved in cell survival (e.g. inflammasome, histone modification).

As is the case for all supplements, not all products are created equal. The main challenge in exogenous ketone products is ensuring that they are effective at increasing blood BHB, that BHB is steadily delivered to the brain, and that these effects are sustained for as long as possible.

There are myriad products touting exogenous ketones on the market. Truth be told, most are hastily formulated, doctored with additives to improve flavor, or inadequately dosed to reap benefit. Just like other supplements on the market, exogenous ketone products should be carefully vetted and come only from trusted manufactures that ideally also test their products. Another tip is to look in the Methods section of an exogenous ketone research study to see which product was used for the study. I’ll present a few specific products below.

Clinical Trials

To learn how exogenous ketones are handled by the body, a 2017 study of 15 healthy individuals consumed a drink containing ketone esters (KE, from TΔS) or ketone salts (KS, from KetoForce). These supplements contained 12-24g of BHB. Both products increased blood levels of BHB. However, the esters (KE) increased blood BHB > 50% more than the KS drink. This also coincided with slower metabolism and excretion. These effects were consistently maintained when drinks were taken regularly around a normal meal pattern, or when administered continuously using a nasogastric tube. With food consumption, BHB levels quickly dropped.

Thirty-six healthy individuals were given a drink of Ensure that contained a ketone ester (from TΔS ) consumed in 3 divided doses. The group was given either low dose (420 mg/kg body weight/day), moderate dose (1071 mg/kg bw/day), or high dose ester (2142 mg/kg bw/day). The high dose group experienced many, significant gastrointestinal side effects that subsided in a matter of days. The ketone ester drink increased plasma levels of the ketones within 1.5 to 2 hours and raised BHB levels.

In 2004, a study of 20 Alzheimer patients consuming a drink containing 40g of emulsified MCTs (from NeoBee) or placebo. Ninety minutes after ingestion, BHB was increased in those who consumed the MCT drink, and these values were positively correlated with improvement in paragraph recall. The effects varied however depending on whether the individual had the APOE4 gene or not.

Can I Eat Normally and Take Exogenous Ketones?

In short, yes. Conversion of supplemented ketone salts and esters to BHB is not inhibited by carbohydrates. However the benefits are stunted if exogenous ketones are taken together with a high carbohydrate diet. While eating carbohydrates won’t undo the effects of exogenous ketones entirely, blood levels of β-hydroxybutyrate will be even greater when the carbohydrate load is reduced. Whereas traditional ketogenic diets require less than 15-10% of caloric intake from dietary carbohydrate, low carbohydrate diets with exogenous ketones may allow for less than 30% from carbohydrate.

Bottom Line

Exogenous ketone products provide an effective means to achieve therapeutic ketosis without strict dietary change. The clinical studies thus far are very promising and these products appear to be safe at reasonable doses. Gastrointestinal side effects are common but can be reduced by slow titration of the product or will resolve on their own with time. They are effective at increasing blood levels of BHB, and this increase is sustained best in ketone ester products dosed between 20-25 g. Ketone salts also increase blood BHB but require higher dosing and divided doses. MCT products are also effective at increasing BHB and should be dosed like salts.

 

How to Choose a Ketone Product

Ketone esters are available commercially from HVMN (a TΔS product) and KE4, which was a crowdfunded project. As these products are the best at increasing blood BHB, they also carry the highest price tag.

Second tier exogenous ketones include the salts. KetoForce and GoBHB are two commercially available, quality ketone salts. You can find ketone salts in the FullScript Dispensary or Natural Dispensary through this site. Look for Keto-Nootropic from Designs for Health.

For lower budgets, MCT products also have benefit but may require higher dosing. Choose Pure C8 from KetoSource which is the most effective at increasing blood ketones and is a thoroughly tested MCT product.

If using any of these products, start by dosing small to avoid gastrointestinal upset. Gradually increase the dose until GI tolerance is achieved. Take these products away from meals and consume a regular low carbohydrate diet.

Have you experimented with exogenous ketones? Tell us in the comments.

Kovács Z. et al (2019) Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature. Front Psychiatry. 10:363.

Stubbs BJ, et al (2017) On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 8:848.

Hashim SA & VanItallie TB (2014) Ketone body therapy: from the ketogenic diet to the oral administration of ketone ester. J Lipid Res. 55(9):1818-26.

Achanta, L. B., & Rae, C. D. (2016). β-Hydroxybutyrate in the Brain: One Molecule, Multiple Mechanisms. Neurochemical Research, 42(1), 35–49.