By: Robert A. Schinetsky

 No matter where you turn these days or what industry you’re involved in, ketogenic diets seem to be the “hot” thing. Be it top-tier athletes, billionaire CEOs, or cinema stars, everyone is hoping on the keto bandwagon and giving carbohydrates the boot.

 Yes, it’s true.

 Fat, once the most loathed of all macronutrients, has been anointed king of the nutritional and fitness hemisphere, and the humble carbohydrate has been relegated to nothing more than waistline-expanding, diabetes-inducing ne’er-do-wells.

 We’re now inundated with full fat this, and zero carb that, with resounding endorsements that fat is a “cleaner” fuel for our bodies -- one that will lead to superior health and otherworldly athletic performance.

 Given this boon in all things keto, there’s a market ripe for exploiting, and supplement companies are salivating at their prospects.

 Over the past year, the market has been inundated by a swarm of ketogenic supplements touted to improve performance, stave off fatigue, and enhance lean mass gains, all with nary a carbohydrate in sight.

 (Interestingly enough, these same claims were made by companies touting carbohydrate-based formulas just a few years prior. But, that’s a story for a different article.)

 Today, we’re here to see what the research has to say regarding any potential benefits of these ketogenic supplements.

 But first, let’s take a look at the “backbone” or foundation of what 99.9% of all keto supplements are built upon -- BHB salts.

 What is BHB?

 BHB stands for beta hydroxybutyrate.

 It is one of the three ketone bodies your body makes from the digestion of dietary fat. BHB serves as an energy molecule in the body, similar to glucose. The difference being that glucose is derived from carbohydrates and BHB (and other ketone bodies) are derived from fat.

 Speaking of other ketone bodies, BHB isn’t the only one. In fact, there are three different ketones your body can make from fats, including:

            - BHB -- The most abundant, and well known, of the ketone bodies that accounts for 78% of the total ketones in the blood.[2] It can also been found under the names: 3-hydroxybutyric acid and 3-hydroxybutanoic acid (3HB)[1]

           - Acetoacetate (AcAc) -- second most plentiful ketone body, accounting for roughly 20% of total ketones in the blood.

           - Acetone -- least abundant ketone accounting for around 2% of ketones in the blood.

 The body can use both BHB and Acetoacetate for energy production, but does not use acetone.

 Now, back to BHB and why it’s in your supplement…

 The body will naturally generate BHB when it is lacking glucose and it will be used to power the various physiological processes in your body, which glucose usually fuels. These various processes also include intense exercise, which is why you’re starting to see various forms of BHB popping up in pre, intra, and post workout supplements.

 You see, when you’re transitioning from a carb-burning athlete to a fat-burning one, the transition takes some time, and during this transitional period, performance, endurance, strength, and power all take a severe hit.

 The thinking behind including these supplemental (exogenous) ketone bodies is that by flooding your body with ketones, it eases the transition and helps you become a fat-fueled athlete much more quickly and without as tremendous of a drop off in performance.[4]

 Speaking of supplements, the way you make an exogenous ketone is by binding it to a mineral, such as sodium, calcium, or magnesium. As such, you’ll typically see these exogenous ketones included in your pre or intra workout in the form of BHB sodium, BHB calcium, or BHB magnesium. Binding it to a mineral makes it more stable in solution and more readily absorbed by the body.

How Does BHB Produce Energy?

 So, if the whole benefit of BHB is to more or less “replace” glucose as the primary fuel in the body, how does it actually produce energy?

 Well, when BHB is ingested, the bond binding it to the mineral salt is cleaved and the BHB molecule is sent into the bloodstream. Upon entering a cell, it heads for the mitochondria (the “nuclear reactor” of a cell that produces energy) where its carboxyl acid group is cleaved, transforming BHB into acetoacetate.[3]

 Acetoacetate then turns into acetoacetyl-CoA, which is yet again cleaved to form the final ketone body, acetone and acetyl-CoA. And it is here that we finally arrive at the goal of using BHB salts -- Acetyl-CoA.

 Acetyl-CoA donates its acetyl group to the citric acid cycle (Krebs cycle) to be oxidized (burned) for energy production, giving us ATP -- the cellular energy currency.[4] Your body then use this ATP to power your muscles for whatever type of exercise you may be performing.

 Now, this all sounds well and good, especially if you’ve been intrigued by the ketogenic diet and want to see how it could potentially enhance your performance and body composition. But, does the theory behind these supplemental ketones actually translate to better performance?

 Let’s find out!

Ketone Supplement Research

 With the increased popularity of ketone supplements hitting the market, researchers have began to investigate whether or not these fat-fueled products actually deliver on they hype.

 Unfortunately, the research results aren’t too favorable, especially if you’re engaged in high-intensity exercise.

Study #1

 For the first study, 10 adult men of similar build and athletic skill were recruited to take part in 2 separate experimental trials. On testing days, participants reported to the lab in the fasted state and consumed either 0.3 g/kg βHB ketone salts or a flavor-matched placebo 30 minutes prior to engaging in cycling exercise.

 FYI, 0.3g/kg BHB would be equivalent to around 24.5 grams of BHB. That’s roughly 2-4 times as much as you’re going to get in an over-the-counter BHB supplement found at your local supplement shop.

 For the testing, the men performed bouts of cycling at 30%, 60%, and 90% ventilatory threshold (VT) followed by a 150-kJ cycling time-trial. Unsurprisingly, total fat oxidation (fat burning) was greater when the men consumed the BHB salts than the placebo. When it came time to measure performance, researchers noted that the men using BHB had a 7% drop in their average power output.[5]

 In other words, supplementing with BHB salts may cause you to lose some of your “top end” during exercise.

 Study co-author commented on the results, saying:

 “Elevated blood ketones seem to inhibit the body's use of glycogen, the stored form of glucose, and favors burning fat instead. That means that the body's quick-burning fuel cannot be accessed during high-intensity bursts of activity."[6]

Study #2

 A second study investigating the effects of exogenous ketone salts was published recently in the June 2018 issue of Medicine & Science in Sports & Exercise. This double-blind, randomized crossover trial involved 11 male team sport athletes and had them perform the Loughborough Intermittent Shuttle Test, which consists of two parts:

        - Part A: 5x15 min intermittent running

        - Part B: shuttle run to exhaustion

 Athletes also had to perform a cognitive test battery before and after the shuttle test as well.[7]

 For the two trials, subjects consumed either a

        - 6.4% carbohydrate-electrolyte solution, or

        - 750 mg⋅kg−1 of exogenous ketones

 before and during exercise.[7]

 To assess the athletes’ performance, researchers tracked heart rate, rating of perceived exertion (RPE), and 15 meter sprint times as well as the men’s blood levels of glucose, lactate, and β-hydroxybutyrate (βHB).

 At the conclusion of the two trials, researchers noted that while the BHB treatment resulted in lower concentrations of plasma glucose and lactate, BHBs did NOT significantly improve heart rate, rating of perceived exertion, 15 meter sprint times or shuttle run time to exhaustion.[7]

 The one area where there was mild benefit from exogenous ketones was in the area of cognitive function where supplementation with BHB attenuated the decline in executive function following the shuttle test.

So, it would appear that while BHB salts don’t enhance high-intensity exercise performance, it might improve brain function following exercise. However, another more recent study calls even that finding into question…

Study #3

 A July 2018 study published in Applied Physiology and Metabolism involving 15 healthy, college-aged men sought to investigate the effects of 11.38 grams of BHB on cognitive and performance measures during a bout of repeated Wingates.[8]

 In case you’re not sure what a Wingate test is, it’s one of the most frequently used exercise protocols for measuring peak anaerobic power and anaerobic capacity. It’s typically performed on a cycle ergometer and involves you pedaling essentially as fast and hard as you can.

 Subjects performed the Wingate test on three separate occasions. The first was to establish a baseline and familiarize subjects with the test. The second and third trial were after the men had fasted for 10 hours, and they consumed either a placebo or 11.38g of BHB salt drink 30 minutes prior to the test.

 Following ingestion of the drink, the men completed a “cognitive challenge”, which consisted of a 5-min FitLight response task while cycling. After the cognitive test ended, the men then performed four 15 second repeated Wingates, resting 4 minutes between each bout. At the conclusion of the sprints, the men had to perform another 5 minute FitLight cognitive test.

 After all the tests were completed and data collected, tabulated, and analyzed, researchers noted that BHB did not significantly improve power output compared to placebo. Additionally, when the men did consume BHB they had a higher fatigue index, which essentially means that they got tired a whole lot faster during sprinting compared to when they drank the placebo.[8]

 Regarding the cognitive tests, BHB also failed to show any improvement in performance compared to the placebo.

Takeaway

 So, what can we gather from these tests?

 Well, it seems pretty clear that when it comes to high-intensity exercise exogenous ketone supplements don’t appear to be all that effective at improving performance. Now, keto proponents may argue that these athletes aren’t truly “fat adapted”, which could partially explain why their power output was so low.

 However, a 2018 study had athletes follow a low-carbohydrate, ketogenic diet (Carbs <50 g/day and <10% of energy from carbohydrates) or a standard high carb (6-10 g/kg/day carbohydrate) for four days. Energy intake was the same between the groups.

 Anaerobic exercise performance was evaluated via Wingate anaerobic cycling test as well as the “yo-yo” intermittent recovery test. Athletes on the keto diet had a 7% lower peak power and 6% lower mean power during the Wingate test.[10] Keto athletes also had a 15% lower total distance ran in the yo-yo intermittent recovery test as well.[10]

 Now, you might say four days isn’t enough to really become fat-adapted, but according to urine tests, athletes on the keto diet were excreting ketones, indicating they had shifted to burning fat for fuel.

 Outside of this study, no other studies have been conducted to date in fat-adapted athletes using exogenous ketones performing high-intensity exercise. So, until that happens, the takeaway is that if you’re a fast-twitch athlete performing repeated bouts of high-intensity exercise, you’d be best served to steer clear of BHB supplements and not fall for the marketing hype.

 If you need further proof that BHB salts aren’t that effective, a recent review assessing the effectiveness of BHB salts and ketone supplements in regards to exercise performance had this to say:

 “However, ketone bodies have also been shown to reduce circulatory FFA availability via inhibiting the lipolytic effect of catecholamines [28], and/or via stimulation of hyperinsulinemia, which subsequently reduces lipolysis [25]. Fe´ry and Balasse [45] reported that the intravenous administration of ketone bodies during exercise attenuated the exercise-mediated increase in circulating FFA and glycerol availability, suggesting that ketone bodies may have suppressed the lipolytic effect of exercise [45]. More recently, bOHB has been demonstrated to inhibit adipocyte lipolysis in vitro via the nicotinic acid receptor protein upregulated in macrophages by interferon-c (PUMA-G/HM74a) [91].”

 In other words, supplementing with ketones reduces the availability of free fatty acids in the bloodstream, meaning you’re hindering your body’s ability to run on its own fat stores.

 The same researchers also concluded that:

 “...there is currently no evidence to support the use of ketone bodies as an ergogenic aid under conditions where optimal evidence based nutritional strategies are applied.”[9]

 Despite ketone supplement popularity, definitive scientific proof of their effectiveness is lacking! At present, there is no data available to suggest that ingestion of ketone supplements before or during exercise increases exercise performance.

References

1. National Center for Biotechnology Information. PubChem Compound Database; CID=441, https://pubchem.ncbi.nlm.nih.gov/compound/441
2. Sena, S. F. (2010). Beta-hydroxybutyrate : New Test for Ketoacidosis. Department of Pathology and Laboratory Medicine.
3. Rojas-Morales, P., Tapia, E., & Pedraza-Chaverri, J. (2016). β-Hydroxybutyrate: A signaling metabolite in starvation response? Cellular Signalling, 28(8), 917–923.
4. Evans, M. , Cogan, K. E. and Egan, B. (2017), Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol, 595: 2857-2871. doi:1113/JP273185
5. O’Malley, T., Myette-Cote, E., Durrer, C., & Little, J. P. (2017). Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males. Applied Physiology, Nutrition, and Metabolism, 42(10), 1031–1035. https://doi.org/10.1139/apnm-2016-0641
6. https://www.medicalnewstoday.com/articles/319742.php
7. Evans, M., & Egan, B. (2018). Intermittent Running and Cognitive Performance after Ketone Ester Ingestion. Medicine and Science in Sports and Exercise. https://doi.org/10.1249/MSS.0000000000001700
8. Waldman, H. S., Basham, S. A., Price, F. G., Smith, J. W., Chander, H., Knight, A. C. McAllister, M. J. (2018). Exogenous ketone salts do not improve cognitive responses after a high-intensity exercise protocol in healthy college-aged males. Applied Physiology, Nutrition, and Metabolism, 43(7), 711–717. https://doi.org/10.1139/apnm-2017-0724
9. Pinckaers PJM, Churchward-Venne TA, Bailey D, van Loon LJC. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Sports Medicine (Auckland, N.z). 2017;47(3):383-391. doi:10.1007/s40279-016-0577-y.
10. Kymberly A. Wroble, Morgan N. Trott, George G. Schweitzer, Rabia S. Rahman, Patrick V. Kelly, Edward P. Weiss. Low-carbohydrate, ketogenic diet impairs anaerobic exercise performance in exercise-trained women and men: a randomized-sequence crossover trial. The Journal of Sports Medicine and Physical Fitness, 2018; DOI: 23736/S0022-4707.18.08318-4