Recently, two published studies investigated the effects of ketone salts in athletes (total n = 22).8,9 Performance over a four-minute cycling time-trial and a 150 kJ ( ~11 mins) cycling time trial were compared between ketone salts vs. carbohydrate. In the four-minute trial there was no change in performance, and in the 150 kJ test, performance decreased by 7%. Blood BHB levels peaked at 0.6 and 0.8 mM in these studies.
That’s not to say that the supplements don’t work. They very well might. But they could also be useless—or even dangerous, says Christine Palumbo, RDN, Nominating Committee member for the Academy of Nutrition and Dietetics. As of right now, there’s no way to know. “Currently, there’s just not enough evidence from research studies to answer those questions,” Barnes adds.
Intermittent fasting will significantly help the body transition into ketosis as limiting your consumption of food for that many hours will help deplete the system of any excess glucose. It’s a shock to the system and research has shown that daily fasting can have other profound effects aside from weight control such as autophagy, lowering risks of heart disease and diabetes, as well as an improvement in cognitive function. So if you’re still wondering how to get into ketosis in 24 hours, then fasting will surely kick things into gear!
An alternative to the ketogenic diet is consumption of drinks containing exogenous dietary ketones, such as ketone esters (KE) and ketone salts (KS). The metabolic effects of KS ingestion have been reported in rats (Ari et al., 2016; Kesl et al., 2016; Caminhotto et al., 2017), in three extremely ill pediatric patients (Plecko et al., 2002; Van Hove et al., 2003; Valayannopoulos et al., 2011) and in cyclists (O'Malley et al., 2017; Rodger et al., 2017). However, the concentrations of blood βHB reached were low (<1 mM) and a high amount of salt, consumed as sodium, potassium and/or calcium βHB, was required to achieve ketosis. Furthermore, dietary KS are often racemic mixtures of the two optical isoforms of βHB, d-βHB, and l-βHB, despite the metabolism of l-βHB being poorly understood (Webber and Edmond, 1977; Scofield et al., 1982; Lincoln et al., 1987; Desrochers et al., 1992). The pharmacokinetics and pharmacodynamics of KS ingestion in healthy humans at rest have not been reported.
The concentrations of blood d-βHB after KE drinks were highly repeatable whether consumed whilst fasted or fed (Figures 4F,G). The d-βHB Cmax values ranged from 1.3 to 3.5 mM when fed and 2.3 to 4.7 mM when fasted. There was no significant effect of visit order on d-βHB kinetics, with the maximal difference in d-βHB Cmax reached by one individual being 1.2 mM when fed and 1.9 mM when fasted. Approximately 61% of the variation in the data was attributable to feeding (fed vs. fasted), <1% to visit order, 16% to inter-participant variability, and the residual 24% variability due to non-specific random effects.
Let’s briefly discuss some organic chemistry. Two molecules that are “the same” but mirror images of each other (like your hands) are known as enantiomers, a type of spatial isomer. Beta hydroxybutyrate comes in two forms, D-β-hydroxybutyrate (“right-handed”) and L-β-hydroxybutyrate (“left-handed”). D-β-hydroxybutyrate is the form that is naturally produced in the body and is most bioavailable when taken exogenously.
The second ketone ester compound was developed at the University of South Florida. This is a diester of AcAc and BDO. In rodents, this ketone ester raises blood D-BHB to 1-4 mM and blood AcAc to up to 5 mM.19 There is one published study of this ketone ester in humans; results showed a 2% decrease in 31 km cycling time trial performance.16 This may be due to the high rate of side effects of this ester studied. Other factors may have been low levels of BHB (<2 mM), the short, high-intensity time trial used, or the use of AcAc vs. BHB.
Exercising is undoubtedly important when it comes to losing weight. An added bonus of being in a state of ketosis is the ability to improve your exercise performance, but you should also remember that entering ketosis for the first time can be a bit of a challenge for a lot of people. The body is still adjusting to such a dramatic diet change, so exercising may prove to be difficult at first. The key here is to keep going.
Ketogenic diets have been successfully used to treat diseases that have an underlying metabolic component, effectively decreasing seizures in recalcitrant pediatric epilepsy (Kossoff et al., 2003), lowering blood glucose concentrations in type 2 diabetes mellitus (Feinman et al., 2015) and aiding weight-loss (Bueno et al., 2013). Emerging evidence supports several clinical uses of ketogenic diets, for example in neurodegenerative diseases (Vanitallie et al., 2005), specific genetic disorders of metabolism (Veech, 2004) and as an adjunct to cancer therapy (Nebeling et al., 1995). Ketone bodies themselves may underlie the efficacy of the ketogenic diet, either through their role as a respiratory fuel, by altering the use of carbohydrate, protein and lipids (Thompson and Wu, 1991; Cox et al., 2016), or through other extra- and intracellular signaling effects (Newman and Verdin, 2014). Furthermore, ketone metabolism may offer a strategy to improve endurance performance and recovery from exercise (Cox et al., 2016; Evans et al., 2017; Holdsworth et al., 2017; Vandoorne et al., 2017). However, achieving compliance to a ketogenic diet can be difficult for both patients and athletes and may have undesirable side effects, such as gastro-intestinal upset (Cai et al., 2017), dyslipidemia (Kwiterovich et al., 2003) or decreased exercise “efficiency” (Edwards et al., 2011; Burke et al., 2016). Hence, alternative methods to raise blood ketone concentrations have been sought to provide the benefits of a ketogenic diet with no other dietary changes.
All of the data I’ll present below were from an experiment I did with the help of Dominic D’Agostino and Pat Jak (who did the indirect calorimetry) in the summer of 2013. (I wrote this up immediately, but I’ve only got around to blogging about it now.) Dom is, far and away, the most knowledgeable person on the topic of exogenous ketones. Others have been at it longer, but none have the vast experiences with all possible modalities (i.e., esters versus salts, BHB versus AcAc) and the concurrent understanding of how nutritional ketosis works. If people call me keto-man (some do, as silly as it sounds), they should call Dom keto-king.
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