Exogenous Ketones-Claims vs Reality with Brendan Egan, PhD. #194
Episode overview:
Brendan is an Associate Professor of Sport and Exercise Physiology, and currently Head of School for the School of Health and Human Performance at DCU. His current research investigates skeletal muscle function and adaptation across the life course, with special interest in the synergy between nutrition and exercise interventions ranging from athletes to older adults. His research group performs human trials involving both acute and chronic interventions for outcomes around performance (physical and cognitive), recovery and adaptation, and have employed a wide range of experimental designs, and have been complimented by molecular analysis tools include transcriptomics, proteomics and metabolomics. Nutrients recently and presently under investigation include caffeine, creatine, omega-3 fatty acids, resveratrol, leucine, protein hydrolysates, beetroot juice, and exogenous ketones.
Brendan received his BSc Sport and Exercise Science from the University of Limerick in 2003, MSc Sport and Exercise Nutrition from Loughborough University in 2004, and PhD from Dublin City University in 2008, before completing two years of post-doctoral training with Prof. Juleen Zierath’s Integrative Physiology group at the Karolinska Institute, Sweden. His doctoral studies focussed on skeletal muscle adaptation to exercise, and in particular the continuity between acute molecular responses to individual bouts of exercise and adaptations induced by exercise training, whereas his post-doctoral training utilised animal models and in vitro cell systems to investigate the transcriptional regulation of skeletal muscle development and mechanisms of insulin resistance. He joined the faculty in the School of Public Health, Physiotherapy, and Sport Science at University College Dublin in 2011, where he spent five years before moving to DCU. He is also currently a Visiting Research Scientist at the Florida Institute for Human and Machine Cognition, Pensacola, FL USA, and a Principal Investigator at the National Institute for Cellular Biotechnology at DCU.
Outside of academia, through his sporting career as an inter-county Gaelic footballer with Sligo from 2003 to 2017, Brendan has had a lifelong association with sport, training and performance at all levels of competition from grassroots to elite level, and also practices in the field as a performance nutritionist with emphasis on field-based team sports, and endurance athletes.
Episode highlights:
(25:27) The “preferred energy source”: media sources, ketones become the dominant fuel in the brain during starvation, dominant does not mean preferred, ketogenesis is a survival mechanism, exogenous ketones can rescue heart failure
(35:30) Ketones as glycogen sparing: Tour de France background, mechanistic basis, two existing relevant studies, one showed glycogen sparing and one showed no difference, differences in methods, the theory is solid but the proof is lacking
(57:27) Ketones for protein generation study: design, downstream markers from mTOR increase with ketones, protein synthesis was not measured directly but is likely, once again the mechanistic theory is promising but the proof is pending, ketones for sleep
Our conversation:
(0:00) Introduction: recent ketone hype, a myriad of purported claims, unique KoopCast format reviewing popular ketone claims, introducing Brandan, putting claims in context and goal takeaways, stay tuned for the outro
(4:12) Brendan’s academic background: research credentials, starting a lab manager, collaborators, working with a wide field of scope to tackle interesting questions
(7:42) Supplement research: investigating the cutting edge of the sports intervention market to stay ahead
(8:56) Studying ketones: MMA example, impetus for 2015-2016 ketone study, research necessarily lags behind practice
(11:48) Ketones and running economy: Aidan Brady and Brendan’s new study, lack of research studying ketones in isolation, theoretical potential for ketones to improve running economy:
(14:35) Design and methods: studying ketones in isolation, treadmill test design, athletes who took ketones saw improvements in running economy via reduced oxygen demand, ketones only performed the same or better than ketones with carbs
(17:17) Koop’s takeaways for ketones and running economy: significance in the marathon world
(18:05) Future research on ketones and running economy: athletes are likely to co-ingest with carbs, what happens if you run on ketones alone, testing the metabolic and GI responses during submaximal testing
(20:07) Challenges with testing ultra endurance: small sample size, Louise Burke example, elite athletes and structured training
(22:22) Setup for special KoopCast format: KoopCast #180 with Chiel Poffe on ketones, exploring research through marketing claims, marketing tends to exaggerate, format overview
(25:27) The “preferred energy source”: media sources, ketones become the dominant fuel in the brain during starvation, dominant does not mean preferred, ketogenesis is a survival mechanism, exogenous ketones can rescue heart failure
(29:08) Endogenous ketones: it is unlikely that ketones are preferred energy sources in athletes, fasting and recovery study, in extreme circumstances ketones are reserved for the brain
(30:53) Exogenous ketones for athletes: the hype comes from a 2016 with unusually high (16-18%) ketone usage, when the same group redid the study they found ~5%, possibly up to 10% but ketones are not preferred
(32:42) Ketones as a non-competitive fuel source: the 10% extra energy intake may be additive, argument for ketones and support from the running economy study, GI distress, ketones are cost-prohibitive
(35:30) Ketones as glycogen sparing: Tour de France background, mechanistic basis, two existing relevant studies, one showed glycogen sparing and one showed no difference, differences in methods, the theory is solid but the proof is lacking
(39:14) Multifactorial approach to ketones: grocery store example, ketones affect multiple processes, interest beyond the field of performance
(41:58) Ketones for cognition: statistically significant reduction in poor decision making in sport, RPE and concentration, application to ultras, mixed results and weak results in research
(44:27) Ultramarathon-specific study: Research Essentials with Chiel Poffe, a $400-500 intervention, prevention of cognitive decline, groups were not isocaloric, mechanistic interest, link in the show notes
(45:51) Ketones for improving training adaptive response: the reason for high interest, claim of increased EPO levels, sources
(47:58) Ketone esters for increased EPO: study design, ketones do increase EPO, it is not yet clear if this is significant, altitude training example, follow-up training studies
(50:30) Angiogenesis study: more information in KoopCast #180, the challenge with non-isocaloric methods
(52:00) Altitude analogy for ketone EPO: altitude is a much greater stimulus and requires hundreds of hours of exposure to be useful, airplane passenger analogy
(53:43) Cost of ketone interventions: year-long example, ketones are cost-prohibitive
(55:01) Ketones for muscle protein synthesis: source, increases in protein generation during a recovery protocol, mechanistic theory
(57:27) Ketones for protein generation study: design, downstream markers from mTOR increase with ketones, protein synthesis was not measured directly but is likely, once again the mechanistic theory is promising but the proof is pending, ketones for sleep
(1:00:34) Forms of ketones: the field changes constantly, “rapid and deep ketosis” curve to shallow and long curve example
(1:02:46) Unpacking the ketone diol advertisement: claims that ketone esters have negative or negligible effects, claims that ketone diols are better for physically and mentally demanding tasks
(1:04:55) Ketone esters and ketone diols: all aforementioned studies used ketone esters, other ketone supplements, esters are employed because ketones in their pure form are hard to digest, mechanism of ketone ester digestion
(1:07:58) Ketone diols: studies with just butanediols showed no improvement and a potential narcotic effect, ketone diols are just half of the ketone ester, the claims in the ad are entirely unsupported
(1:09:57) Recap of ketone chemistry: HVMN Ketone-IQ is the diol, original HVMN product is ketone esters, Delta G is ketone monoester
(1:11:04) Why is HVMN marketing diols: diols are less well studied and less effective, they are also much cheaper, feel-good drugged effect of high butanediol consumption, KetoneAid ester and butanediol products
(1:14:09) Practical challenges: potential performance benefits are in a small range of ketone blood concentrations, practical challenges of implementing ketones with precision, the value proposition may or may not be worth it
(1:16:59) Wrap-up: where to find Brendan’s research, banter
(1:18:41) Outro: giving thanks, preface for Koop’s commentary on the ketone space
(1:19:26) Ketones are not a viable ergogenic aid: research does not currently support ketone use in endurance sports, even if it did the high potential for error makes pulling this off impractical
(1:21:41) Ketones might be an adaptive aid: the research is still inconclusive, the only risk is financial, ketones for training are fine but not a priority
(1:22:26) Marketing of ketones: disingenuous at best, ketone companies know better, analogy and theoretical personal example of advertising coaching Western States winners, steer clear of disingenuous marketing and uninformed influencers
Additional resources:
Papers discussed-
Exogenous ketone Supplements in Athletic Contexts: Past Present and Future
Ketone monoester ingestion increases postexercise serum erythropoietin concentrations in healthy men
The Effect of Novel Exogenous Ketone Supplements on Blood Beta-Hydroxybutyrate and Glucose
HVMN Keton IQ vs original product claims
Delta G claims (scroll to bottom)
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