The Latest Research on Exogenous Ketones and Other Performance Enhancers

April 24, 2019

Back on the podcast today, we have researcher and athlete Brianna Stubbs, PhD. Brianna has been a world-champion rower and is now competing in cycling, running, and triathlon. She is also Research Lead for HVMN, advancing the science on human optimisation and creating content and products to improve physiology, metabolism, and cognition.

As a world expert on ketone metabolism, Brianna is here with me to talk about the latest research on exogenous ketones. We discuss their effects on athletic performance, brain injury, and cognition, and she weighs in on the controversy regarding the effect of ketone esters on the inflammasome. We also look at the misunderstood role of lactate and how it’s now being used to improve athletic performance.

Here’s the outline of this interview with Brianna Stubbs:

[00:00:35] Our previous podcasts with Brianna: 1, 2, 3.

[00:02:00] Podcast: Professor Tim Noakes: True Hydration and the Power of Low-Carb, High-Fat Diets.

[00:02:19] Andrew Bosch at the University of Cape Town.

[00:05:03] Training for full Ironman.

[00:05:19] Podcast: Off Road Triathlon World Champion Lesley Paterson on FMT and Solving Mental Conundrums.

[00:07:39] Using ketone esters to fuel for a race.

[00:10:18] Who's using the ketone ester?

[00:11:08] Effects of ketone esters on cognitive function; Study: Evans, Mark, and Brendan Egan. "Intermittent Running and Cognitive Performance after Ketone Ester Ingestion." Medicine and science in sports and exercise 50.11 (2018): 2330-2338.

[00:12:21] Rescue of ATP in the brain of mice given exogenous ketones; Study: Prins, M. L., et al. "Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats." Journal of neurochemistry 90.3 (2004): 666-672.

[00:13:46] Unpublished research on ketone esters in hypoxia: Ketone Esters for Optimization of Cognitive Performance in Hypoxia.

[00:15:33] One hour cycling record; Vittoria Bussi.

[00:16:00] Bradley Wiggins; The Flying Scotsman Graeme Obree; Jens Voigt.

[00:19:19] Professor Tim Noakes; Central governor model of fatigue: Noakes, Timothy D. "The central governor model of exercise regulation applied to the marathon." Sports medicine 37.4-5 (2007): 374-377.

[00:19:32] Cyclists go slower from the first pedal stroke when you put them in a hot laboratory; Study: Tucker, Ross, et al. "The rate of heat storage mediates an anticipatory reduction in exercise intensity during cycling at a fixed rating of perceived exertion." The Journal of physiology 574.3 (2006): 905-915.

[00:19:43] Cold water in mouth reduces perceived effort and improves performance. Study: Burdon, Catriona A., et al. "The effect of ice slushy ingestion and mouthwash on thermoregulation and endurance performance in the heat." International journal of sport nutrition and exercise metabolism 23.5 (2013): 458-469.

[00:19:57] Cooling mouthwash improves performance; Study: Jeffries, Owen, Matthew Goldsmith, and Mark Waldron. "L-Menthol mouth rinse or ice slurry ingestion during the latter stages of exercise in the heat provide a novel stimulus to enhance performance despite elevation in mean body temperature." European journal of applied physiology 118.11 (2018): 2435-2442.

[00:22:25] Podcast: Science and Application of High Intensity Interval Training with Paul Laursen, PhD.

[00:22:56] Potential therapeutic applications of ketone esters.

[00:23:43] Ketogenic diet may help with alcohol withdrawal. Study: Dencker, Ditte, et al. "Ketogenic Diet Suppresses Alcohol Withdrawal Syndrome in Rats." Alcoholism: Clinical and Experimental Research42.2 (2018): 270-277.

[00:24:43] Dr. Stephen Cunnane; MCT study: Courchesne-Loyer, Alexandre, et al. "Emulsification increases the acute ketogenic effect and bioavailability of medium-chain triglycerides in humans: protein, carbohydrate, and fat metabolism." Current developments in nutrition 1.7 (2017): e000851.

[00:28:13] Ketone esters as nootropics.

[00:30:23] Mitigating traumatic brain injury (TBI); lactate.

[00:31:41] Improved outcomes with lactate infusion in intensive care; Study: Nalos, Marek, et al. "Half-molar sodium lactate infusion improves cardiac performance in acute heart failure: a pilot randomised controlled clinical trial." Critical care 18.2 (2014): R48; and Ichai, Carole, et al. "Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial." Intensive care medicine 39.8 (2013): 1413-1422.

[00:32:22] Professor George Brooks; Study: Thomas, Claire, et al. "Effects of acute and chronic exercise on sarcolemmal MCT1 and MCT4 contents in human skeletal muscles: current status." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 302.1 (2011): R1-R14.

[00:33:07] Ketones: the ugly duckling of metabolism. Study: VanItallie, Theodore B., and Thomas H. Nufert. "Ketones: metabolism's ugly duckling." Nutrition Reviews 61.10 (2003): 327-341.

[00:34:20] Podcast: Why Cholesterol Levels Have No Effect on Cardiovascular Disease (And Things to Think about Instead), with Dr. Malcolm Kendrick.

[00:35:28] Lactate increase carbohydrate usage and improves performance; Study: Azevedo Jr, John L., et al. "Lactate, fructose and glucose oxidation profiles in sports drinks and the effect on exercise performance." PLoS One 2.9 (2007): e927.

[00:37:24] Cytomax, Muscle Milk.

[00:39:11] L-Lactate vs D-Lactate; D-lactate free probiotics.

[00:40:01] Podcast: How to Use Probiotics to Improve Your Health, with Jason Hawrelak, PhD.

[00:40:44] Butyrate and exogenous ketones; Study: Cavaleri, Franco, and Emran Bashar. "Potential Synergies of β-Hydroxybutyrate and Butyrate on the Modulation of Metabolism, Inflammation, Cognition, and General Health." Journal of nutrition and metabolism 2018 (2018).

[00:41:21] Effect of patents on innovation.

[00:42:34] Richard Stallman, president of the Free Software Foundation.

[00:44:10] Paper recently accepted for journal publication on GI symptoms associated with ketone esters (not yet published).

[00:44:53] Acetoacetate diester causing GI symptoms; Study: Leckey, Jill J., et al. "Ketone diester ingestion impairs time-trial performance in professional cyclists." Frontiers in physiology 8 (2017): 806.

[00:49:45] Study: Dearlove, David James, et al. "Nutritional ketoacidosis during incremental exercise in healthy athletes." Frontiers in physiology 10 (2019): 290.

[00:51:21] Dominick D’Agostino, PhD; β-hydroxybutyrate (BHB) blocks inflammation; Study: Youm, Yun-Hee, et al. "The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease." Nature medicine 21.3 (2015): 263.  

[00:52:32] Newer study showing greater inflammatory response with ketone ester: Neudorf, Helena, et al. "Oral Ketone Supplementation Acutely Increases Markers of NLRP3 Inflammasome Activation in Human Monocytes." Molecular nutrition & food research(2019): 1801171.

[00:53:46] Denmark study on effect of ketones on LPS-induced inflammation: Thomsen, Henrik H., et al. "Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS-induced inflammation in humans: anticatabolic impact of ketone bodies." The American journal of clinical nutrition 108.4 (2018): 857-867.

[00:59:32] How to find Brianna and HVMN: Twitter: @BriannaStubbs and @HVMN; Instagram: HVMN; Website:; HVMN blog.

[01:00:00] HVMN podcast on Apple Podcasts;  HVMN on YouTube.

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