When we say ketones, we are referring to the primary circulating fatty acid metabolites beta-hydroxybutyrate (βOHB) and acetoacetate (AcAc). More on ketone basics here.
Exogenous ketones
(also known as ketone supplements) and well-formulated ketogenic diets share at
least one thing in common. They both result in increased circulating
concentrations of beta-hydroxybutyrate (BOHB), but ultimately are associated
with very different patterns of ketosis, as well as differing metabolic and
physiologic outcomes. In short, they should not be assumed to have equivalent
effects simply because they achieve similar BOHB blood levels. Having said
that, there are many reasons we should continue to study the various forms and
potential applications of ketone supplements.
For the past few
million years, the only way for humans to make use of ketones for fuel was to
restrict carbohydrates low enough and long enough to induce the liver to make
them. This is admittedly hard for many people to do in a world that still
believes that dietary carbs are good and fats are bad. An emerging alternative
is to consume ketones as a dietary supplement. The research into how these
function in the body and what benefits they can confer remains at an early
stage, but there are already a number of such products available for sale. In
this section, we will discuss how exogenous ketones affect blood ketone levels,
and how they may influence health and disease compared to ketones produced
within the body.
The two predominant ketones made by the liver are beta-hydroxybutyrate (BOHB) and acetoacetate (AcAc). Here’s a brief summary of basic information regarding these ketones:
■ It is estimated that a
keto-adapted adult can make 150 or more grams of ketones daily after adapting
to a total fast (Fery 1985), and perhaps 50-100 grams per day on a
well-formulated ketogenic diet.
■ Some AcAc naturally breaks down
to form acetone, which comes out through the lungs and kidneys, giving a
chemical odor to the breath when ketones are high.
■ Much of the AcAc made in the
liver is picked up by muscle and converted to BOHB.
■ As part of the keto-adaptation
process, how muscles and kidneys deal with BOHB and AcAc changes over the first
few weeks and months, and thus the ratio of AcAc to BOHB in the blood changes
considerably in the first week or two.
■ While the ultimate fate of most
ketones in the blood is to be burned for fuel, BOHB and AcAc appear to have
differing roles in regulating genes and cellular functions.
■
Particularly with gene regulation, BOHB seems to play a more significant
regulatory role than AcAc, but AcAc may have a particular role in signaling
muscle regeneration (Zou 2016).
The keto-esters
are more appropriate for delivering higher doses of BOHB, but with repeated
dosing can push the limits of taste and GI tolerance. There has been fairly
extensive research on a compound 3-hydroxybutyl 3-hydroxybutyrate that is
converted via hydrolysis and liver metabolism to yield 2 molecules of ketones,
presumably mostly D-BOHB (Clarke 2012 and 2014). In a study involving lean
athletes, an approximate 50 gram dose raised blood BOHB levels to 3 mM after 10
min and reached 6 mM by 20 min.
Submaximal exercise
resulted in increased ketone disposal from 2 to 3 hours and contributed
significantly to whole body energy use during exercise (Cox 2016). This product
has been shown to significantly reduce appetite after a single dose (Stubbs
2018) but its effect on body weight in humans over a longer period of time has
not been studied, nor has its effect on blood glucose control been reported in
humans with type 2 diabetes. However a single dose prior to a glucose tolerance
test in healthy humans reduced blood glucose area-under-curve by 11% and
non-esterified fatty acid area-under-curve by 44% (Myette-Cote 2018).
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