Ketone supps and physical performance
We've had a couple more studies on the various ketone supps: two esters (D-b-hydroxybutyrate-R 1,2-Butanediol Monoester and R,S-Butanediol Diacetoacetate) and one beta-Hydroxybutyrate sodium and potassium salts (KetoForce). We'll call them Clarke, Burke, and Stewart so I don't get Carpal Tunnel Syndrome typing them out. Technically, b-hydroxybutyrate isn't really a ketone, but whatevs.


"Clarke"


"Burke"


"Stewart" (this is actually a blend of the sodium "Na" and potassium "K" [not shown] salts)


Two studies on Stewart

Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males (O'Malley et al., 2017)

"Ten healthy, recreationally active men." The participants did a brief warm-up then a 150 km cycling time trial after receiving 24 g Stewart or salt-matched placebo.  Controlling for salt was cool, but Stewart has about as 5 kcal/g, so the placebo could've controlled for that somehow, with either fat or carb, or something... (probably wouldn't have mattered anyway)

Results: blood beta-hydroxybutyrate reached about 1 mM, power output declined 7% and it took the keto group about 45 seconds longer to complete the time trial.

Oral beta-hydroxybutyrate salt fails to improve 4-minute cycling performance following submaximal exercise (Rodger et al., 2017)

"Highly trained cyclists." Similar study design as McSwiney's -- drain the tank with 90 minutes cycling at 80% max then 4 minute maximal performance test. Same dose as above in 2 divided doses. Same issue with the control group.

Results: blood beta-hydroxybutyrate reached ~0.6 mM and there was a trivial (non-significant) increase in power. This is actually in line with my interpretation of McSwiney regarding the decline in power output before and after draining the tank; ketoadaptation and all that jazz.


One study on Burke

Ketone diester ingestion impairs time-trial performance in professional cyclists (Leckey et al., 2017)

"Internationally competitive elite cyclists." Two doses of 20 g Burke then a 20-minute warm-up followed by a 31 km time-trial. Non-caloric placebo control, whereas Burke is estimated 4.7 kcal/g. They were well-fed and caffeinated.

Results: beta-hydroxybutyrate reached ~1.1 mM and time-trial took 2% longer and power was reduced 3.7%.


One study on Clarke

Nutritional ketosis alters fuel preference and thereby endurance performance in athletes (Cox et al., 2016)

"High performance athletes." This study was different: one group got a drink that was 40% Clarke and 60% carbs (by calories), the other drink was 100% carbs. Calorie-controlled. They cycled for an hour at 75% max (to drain the tank), then 30-minute time trial.

Results: this is the first one that worked. beta-hydroxybutyrate reached 2-3 mM and they made it 2% further during the time-trial.


Interpretation

The most expensive one won LOL. It's estimated to be around $30 a pop, so maybe worth it for competitive athletes on game day, not every day. To be honest, I think these products should be tested in other contexts, eg, cognitive impairment, other neuro or mood/behavioral conditions, etc.

But why different results? The most obvious confounder was ketonemia: Clarke got beta-hydroxybutyrate to 3 mM -- this smoked the others which ranged from 0.6 to 1.1 mM. Enough to the point where it could considerably alter fuel utilization.

There is also the [theoretical] issue of isomers - endogenous bHB is "D." Stewart and Burke are blends of D-bHB and L-bHB (which is sort of like it's mirror image), whereas Clarke converts exclusively to D-bHB in the body. There are some early studies which showed the natural version "works" better. The studies mentioned above might confirm, although they should really be tested back to back and controlled for the level of ketonemia.

*HOWEVER, Dr. D'Agostino doesn't seem to think D/L matters.

Comparing the esters directly: figuring out the dose might be tricky. Clarke is basically metabolized to two molecules of d-BHB whereas Burke goes to DL-bHB and acetoacetic acid (AcAc), some of the latter can convert to acetone and is lost via breath. Thus, might need a higher dose. Idk.

Here is an analysis of these studies by a company that manufactures Clarke.

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