I wrote this post at about the same time Germany won the World Cup in Rio de Janeiro in 2014. There’s been a lot of moving and shaking in the world of exogenous ketones since then, not to mention soccer. Looking back on my post, I still consider it relevant in terms of what exogenous ketones possibly can (and cannot) do for performance. In this case, to see if exogenous ketone esters provide me a “boost” by allowing me to do the same amount of work while expending less energy (and work at a relatively lower VO2) compared to no supplementation.
Ketones are an alternate energy or fuel source for brain and body that our bodies have naturally produced and used for millennia. Ketones have recently leapt to the forefront of health and wellness conversations worldwide as the scientific body of research that seeks to understand their numerous unique properties and profound systemic effects has begun to grow (see below).
As seen in this exercise, glucose tends to fall quite precipitously following exogenous ketone ingestions. Without exception, every time I ingested these compounds (which I’ve probably done a total of 25 to 30 times), my glucose would fall, sometimes as low as 3 mM (just below 60 mg/dL). Despite this, I never felt symptomatic from hypoglycemia. Richard Veech (NIH) one of the pioneers of exogenous ketones, has suggested this phenomenon is the result of the ketones activating pyruvate dehydogenase (PDH), which enhances insulin-mediated glucose uptake. (At some point I will also write a post on Alzheimer’s disease, which almost always involves sluggish PDH activity —in animal models acute bolus of insulin transiently improves symptoms and administration of exogenous ketones does the same, even without glucose.)
Working memory involves temporarily storing and manipulating information. The game involves seeing three cards – a top card with a symbol that then moves along a track and is flipped over, exposing a new card above. The goal is to remember the symbol of the cards two cards back and indicate whether it matches the visible card or not. If you have ever played dual n-back games, this is very similar.
A lot of people who use ketogenic diets will include a regular (i.e. weekly) carb refeed meal. There are various reasons behind doing this. If you are doing a lot of glycolic based training, then the carb refeed can help bump up muscle glycogen levels and in turn boost performance. Others use these refeeds as a way to keep their thyroid health in check, and finally some people use these refeeds as a ‘cheat day’ – so that they can still enjoy the pleasures from carbohydrates!
Most of the information regarding the effects of ketosis come from studies on the ketogenic diet, wherein ketones are made by the liver and become a major fuel source for the body. The ketogenic diet is currently under investigation for its potential therapeutic effects in a number of healthy and disease states. More recently, studies are beginning to reveal that many of the effects observed with the ketogenic diet are mechanistically attributable to ketones, which is a primary reason that exogenous ketones are being developed and studied. However, because they are such a new technology, there’s not a lot of data on exogenous ketones themselves. In a few pre-clinical studies, exogenous ketones have mimicked the therapeutic effects of the ketogenic diet”
International Patent # PCT/US2014/031237, University of South Florida, D.P. D’Agostino, S. Kesl, P. Arnold, “Compositions and Methods for Producing Elevated and Sustained Ketosis”. P. Arnold (Savind) has received financial support (ONR N000140610105 and N000140910244) from D.P. D’Agostino (USF) to synthesize ketone esters. The remaining authors have no conflicts of interest.
Although most of the research has been done utilizing ketone esters, ketone salt supplementation has the potential to provide additional benefits through the extra electrolytes/nutrients that are required to make the ketones. While ketone esters are expensive due to the manufacturing process involved in making them, ketone salts might be a more convenient option for both inducing a state of ketosis and elevating blood ketone levels for various reasons we will discuss in another article.
There is one viable explanation for consuming ketones. If you're in a calorie or carb-restricted state, then maybe during a workout it would make sense. But even then, that really only applies to endurance activities, since it has more to do with enhancing aerobic performance (where oxygen is required), than it does with enhancing high-intensity efforts (where it's not).
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Effects of ketone supplementation on blood βHB. a, b Blood βHB levels at times 0, 0.5, 1, 4, 8, and 12 h post intragastric gavage for ketone supplements tested. a BMS + MCT and MCT supplementation rapidly elevated and sustained significant βHB elevation compared to controls for the duration of the 4-week dose escalation study. BMS did not significantly elevate βHB at any time point tested compared to controls. b BD and KE supplements, maintained at 5 g/kg, significantly elevated βHB levels for the duration of the 4-week study. Two-Way ANOVA with Tukey’s post hoc test, results considered significant if p < 0.05. Error bars represent mean (SD)
There’s also the issue of supplement safety in general. All supplements—whether you’re talking about vitamins, minerals, herbs, or other nutritional mixes—are only loosely regulated. “We know that there is contamination of supplements here in the U.S., often from products that are manufactured abroad,” Palumbo says. In that case, “the same concerns apply to this as for any other supplement.”
Animal procedures were performed in accordance with the University of South Florida Institutional Animal Care and Use Committee (IACUC) guidelines (Protocol #0006R). Juvenile male Sprague–Dawley rats (275–325 g, Harlan Laboratories) were randomly assigned to one of six study groups: control (water, n = 11), BD (n = 11), KE (n = 11), MCT (n = 10), BMS (n = 11), or BMS + MCT (n = 12). Caloric density of standard rodent chow and dose of ketone supplements are listed in Table 1. On days 1–14, rats received a 5 g/kg body weight dose of their respective treatments via intragastric gavage. Dosage was increased to 10 g/kg body weight for the second half of the study (days 15–28) for all groups except BD and KE to prevent excessive hyperketonemia (ketoacidosis). Each daily dose of BMS would equal ~1000–1500 mg of βHB, depending on the weight of the animal. Intragastric gavage was performed at the same time daily, and animals had ad libitum access to standard rodent chow 2018 (Harlan Teklad) for the duration of the study. The macronutrient ratio the standard rodent chow was 62.2, 23.8 and 14 % of carbohydrates, protein and fat respectively.
As stated above, there appears to be a difference between supplemental and dietary calcium intake, which can be important to keep in mind. One study found aggregate calcium intakes above 1400 mg per day (from dietary and supplemental intake combined) to be associated with higher death rates, cardiovascular disease, and ischemic heart disease in women. A 2014 meta-analysis found an association between dietary calcium intake and cardiovascular mortality. The meta-analysis actually found a u-shaped relationship, where dietary calcium intakes that were both lower and greater than 800 mg/day were gradually associated with increased risk of cardiovascular mortality.
Let’s take a look at some of the facts and misconceptions about three of the minerals used to make ketone mineral salts: sodium, calcium, and magnesium. Potassium is very hygroscopic, meaning that it absorbs water very easily. Therefore, it is only feasible that it can be utilized in liquid formulations. Thus, one should be cautious if companies say they have potassium BHB salt powder in their product. I’d be very surprised if that’s actually the case.
I also concluded that post by discussing the possibility of testing this (theoretical) idea in a real person, with the help of exogenous (i.e., synthetic) ketones. I have seen this effect in (unpublished) data in world class athletes not on a ketogenic diet who have supplemented with exogenous ketones (more on that, below). Case after case showed a small, but significant increase in sub-threshold performance (as an example, efforts longer than about 4 minutes all-out).
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