When we say ketones, we are discussing the key circulating fatty acid metabolites beta-hydroxybutyrate (OHB) and acetoacetate (AcAc). More on ketone basics here. Exogenous ketones (also called ketone supplements) and well-formulated ketogenic diets share at least one thing in common. They both lead to increased circulating concentrations of beta-hydroxybutyrate (BOHB), but ultimately are connected with completely different patterns of ketosis, as well as differing metabolic and physiologic outcomes. In a nutshell, they should not be assumed to have equivalent effects simply because they achieve similar BOHB blood levels. With that in mind, there are many reasons we must continue to study the many forms and potential applications of ketone supplements.

Within the last few million years, the only method for humans to apply ketones for fuel ended up being to restrict carbohydrates low enough and long enough to induce the liver to ensure they are. This is admittedly hard for many individuals to accomplish in a world that also believes that dietary carbs are excellent and fats are bad. An emerging alternative would be to consume ketones as being a nutritional supplement. The study into how these function in your body and what benefits they can confer remains early stage, but we already have several such products on the market. Within this section, we are going to discuss how exogenous ketones affect blood ketone levels, and how they may influence health and disease in comparison to ketones produced within the body.

The two predominant ketones produced by the liver are beta-hydroxybutyrate (BOHB) and acetoacetate (AcAc). Here’s a short review of basic info about these ketones:

It is estimated that a keto-adapted adult can make 150 or more grams of ketones daily after adapting to an overall fast (Fery 1985), and possibly 50-100 grams per day on the well-formulated ketogenic diet.

Some AcAc naturally breaks down to form acetone, which will come out through the lungs and kidneys, giving a chemical odor for the breath when ketones are high.

A lot of the AcAc produced in the liver is found by muscle and converted to BOHB.

As part of the keto-adaptation process, how muscles and kidneys cope with BOHB and AcAc changes over the first few weeks and months, and so the ratio of AcAc to BOHB in the blood changes considerably inside the first week or two.

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As the ultimate fate of most ketones in the blood is going to be burned for fuel, BOHB and AcAc appear to have differing roles in regulating genes and cellular functions.

Particularly with gene regulation, BOHB appears to play a more significant regulatory role than AcAc, but AcAc may have a particular role in signaling muscle regeneration .

Sources and Formulations of Exogenous Ketones – The two compounds commonly referred to as ‘ketone bodies’ (BOHB and AcAc) are made and used for multiple purposes across nature from algae to mammals, but seldom in concentrations useful for extraction as human food. For this reason, the source of many exogenous ketones is chemical synthesis. Furthermore, most current research and make use of of ketone supplements targets BOHB. This is because AcAc is chemically unstable – it slowly breaks down to form acetone by releasing of one molecule of CO2.

In a keto-adapted individual where ketone metabolism is brisk with up to 100 grams or maybe more being oxidized (i.e., ‘burned for energy’) daily, the little amount lost in breath and urine as acetone is minor. But since this breakdown occurs spontaneously without the need for the aid of enzymes, it also transpires with AcAc in a stored beverage or food (even in an air-tight container), making the shelf-life of AcAc-containing products problematic. Thus all current ketone supplements consist of BOHB in certain form instead of uolcok natural combination of BOHB and AcAc produced by the liver.

Another essential distinction between endogenous and exogenous BOHB is that most synthetic BOHB used in dietary supplements is a combination of the two ‘D’ and ‘L’ isomers, whereas endogenously produced BOHB includes just the D-isomer. Metabolically, the 2 isomers are extremely different, and current published information suggests that most of the energy and signaling benefits of BOHB derive through the D-form. This is potentially problematic since the L-isomers are certainly not metabolized using the same chemical pathways since the D-forms (Lincoln 1987, Stubbs 2017), and it remains unclear whether humans can convert the L-form to the D-form.

Thus, while the L-isomers tend not to seem to be toxic, they are certainly not likely to impart the identical benefits because the D-forms. In addition, the current assays for blood ketones are specific for the D-isomer, therefore it is difficult to track blood levels and clearance of the L-isomer taken in a supplement.

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