The ketone esters are, hands-down, the worst tasting compounds I have ever put in my body. The world’s worst scotch tastes like spring water compared to these things. The first time I tried 50 mL of BHB monoester, I failed to mix it with anything (Dom warned me, but I was too eager to try them to actually read his instructions). Strategic error. It tasted as I imagine jet fuel would taste. I thought I was going to go blind. I didn’t stop gagging for 10 minutes. (I did this before an early morning bike ride, and I was gagging so loudly in the kitchen that I woke up my wife, who was still sleeping in our bedroom.) The taste of the AcAc di-ester is at least masked by the fact that Dom was able to put it into capsules. But they are still categorically horrible. The salts are definitely better, but despite experimenting with them for months, I was unable to consistently ingest them without experiencing GI side-effects; often I was fine, but enough times I was not, which left me concluding that I still needed to work out the kinks. From my discussions with others using the BHB salts, it seems I have a particularly sensitive GI system.
I started this website because it was hard to find trustworthy, evidence-based information about the ketogenic diet. Information that was published and peer reviewed by respected scientific journals. After years of research, I'm sure you'll achieve great results in a healthy way following my advice. I do my best to translate scientific research jargon into plain English. Remember, it's always a good idea to consult a doctor before starting a new diet!
The blood levels of BOHB that can be achieved with the salts or ester formulations are in the 1-3 mM range, similar to what can be achieved with a well-formulated ketogenic diet in insulin sensitive humans, but well below levels achieved after a 4-7 days of total fasting (Owen 1969). In more insulin resistant humans, the ester formulation may deliver higher blood levels than a sustainable diet (as opposed to short term fasting). For example, in the Virta IUH Study of over 200 patients with type 2 diabetes, blood ketone mean levels were 0.6 mM at 10 weeks and 0.4 mM after 1 year.
Exogenous ketones can lower appetite during a fast. After an overnight fast, normal weight human subjects either drank a ketone ester supplement or a calorie-matched glucose drink. Compared to the glucose drinkers, the ketone drinkers had lower insulin, lower ghrelin, greater satiety, and less hunger. This can be useful for people trying to extend their fast who don’t want to or can’t yet deal with the hunger. You’re still taking in energy, but the metabolic profile remains similar to that of a fasted person.
As ketone drinks can deliver nutritional ketosis without fasting, we investigated the effect of food on KE uptake and metabolism. It is well documented that food in the gut can slow, or prevent, the uptake of small hydrophilic hydrocarbons, such as βHB (Melander, 1978; Toothaker and Welling, 1980; Horowitz et al., 1989; Fraser et al., 1995), so decreased gut βHB uptake is probably the cause of lower blood βHB following the meal. Despite higher blood βHB concentrations in the fasted state, the meal did not alter plasma AcAc. This suggests that the rate of conversion of βHB to AcAc may not match the rate of appearance of βHB following KE consumption. Alternatively, meal-induced changes in the hepatic ratio of NAD+:NADH may have altered the conversion of βHB to AcAc (Himwich et al., 1937; Desrochers et al., 1992).
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.
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Ketone monoester and diester compounds may circumvent the problems associated with inorganic ion consumption in KS drinks. KE ingestion rapidly increased blood ketone concentrations to >5 mM in animals (Desrochers et al., 1995a,b; Clarke et al., 2012a) and the first oral, non-racemic KE for human consumption, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, raised blood βHB concentrations to 3–5 mM in healthy adults (Clarke et al., 2012b; Shivva et al., 2016) and athletes (Cox et al., 2016; Holdsworth et al., 2017; Vandoorne et al., 2017). However, the pharmacokinetics and pharmacodynamics of this KE with confounding factors, such as prandial state or multiple KE drinks, have not been characterized.
Exogenous ketones are created in a lab to accelerate both physical and mental performance. These ketone drinks were actually used in pro cycling races back in 2015, trading at prices that would make using your kidney as a bartering tool seem like a cut price deal. Fortunately, they’ve now come down in cost and are used often in between meals as a way of blackmailing your body into getting into ketosis way faster.
It’s not clear that the Weir coefficients used to estimate EE are relevant for someone in ketosis, let alone someone ingesting exogenous BHB. (The Weir formula states that EE is approximated by 3.94 * VO2 + 1.11 * VCO2, where VO2 and VCO2 are measured in L/min; 3.94 and 1.11 are the Weir coefficients, and they are derived by tabulating the stoichiometry of lipid synthesis and oxidation of fat and glucose and calculating the amount of oxygen consumed and carbon dioxide generated.) While this doesn’t impact the main observation—less oxygen was consumed with higher ketones—it does impact the estimation of EE and substrate use.
Exogenous ketones cause the body to rely less on fat as fuel (see Fig 3). Fat takes longer to metabolise for energy than muscle glycogen. This is why fatty acids are not the preferred fuel under heavy exercise. This could be useful for keto-adapted athletes performing high-intensity cardiovascular or strength training.12 This is particularly useful for the Keto-adapted athlete who wants to undergo high-intensity cardiovascular or strength training.
Exogenous ketones don’t seem to improve high-intensity, glucose-intensive exercise, increasing fat burning during steady state exercise but dropping top-end high-intensity performance. Another study found that ketone dieters reduced 50-minute time trial performance in cyclists, though another group of researchers have criticized the methods. Even when a ketone ester didn’t improve performance in the shuttle run to exhaustion and 15 meter sprint repeats, it did reduce the drop in brain function following the exercise.
In the second of these posts I discuss the Delta G implications of the body using ketones (specifically, beta-hydroxybutyrate, or BHB, and acetoacetate, or AcAc) for ATP generation, instead of glucose and free fatty acid (FFA). At the time I wrote that post I was particularly (read: personally) interested in the Delta G arbitrage. Stated simply, per unit of carbon, utilization of BHB offers more ATP for the same amount of oxygen consumption (as corollary, generation of the same amount of ATP requires less oxygen consumption, when compared to glucose or FFA).
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