Ketones for Performance, Cognition, and Cardiovascular Health

Researcher and elite athlete Brianna Stubbs is back on the podcast today, checking in before her recent Ironman competition in Santa Cruz, California. Since we last talked with Brianna she’s left HVMN and joined the Buck Institute for Research on Aging as Lead Translational Scientist. There she’ll be studying ketone biology and collaborating on some of the best research being conducted today with the mission of living better, longer.

In this interview, Brianna and I talk about some of the latest studies on ketone metabolism, which continues to show promise for athletic performance, cognition, and cardiovascular health. She also notes where the research in this area is lacking and even contradictory. Brianna also shares her personal strategy for dosing the ketone monoester she helped bring to the marketplace. 

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

[00:00:00] Brianna’s previous podcasts: World Champion Rower and Ketone Monoester Researcher Brianna Stubbs, The D-BHB Ketone Monoester Is Here, Women in Science: Bridging the Gender Gap, and The Latest Research on Exogenous Ketones and Other Performance Enhancers.

[00:02:00] Racing Ironman.

[00:05:10] Lesley Paterson; Podcast: Off Road Triathlon World Champion Lesley Paterson on FMT and Solving Mental Conundrums.

[00:06:57] Dosing the ketone ester during the triathlon.

[00:09:55] Ketone ester as a tool to to evaluate perception of exercise; Study: Faull, Olivia Kate, et al. "Beyond RPE: The perception of exercise under normal and ketotic conditions." Frontiers in physiology 10 (2019): 229. 

[00:11:09] Lead Translational Scientist at the Buck Institute for Research on Aging.

[00:13:01] Dale Bredesen, MD; Eric Verdin, MD.

[00:13:36] Review on ketone metabolism: Newman, John C., and Eric Verdin. "Ketone bodies as signaling metabolites." Trends in Endocrinology & Metabolism 25.1 (2014): 42-52.

[00:14:56] Jeff Volek, PhD, RD & Stephen Phinney, MD, PhD

[00:18:07] STEM-Talk Podcast: Episode 92 with Megan Roberts and Episode 94 with John Newman.

[00:19:27] β-Hydroxybutyrate (BHB), as an endogenous histone deacetylase inhibitor; Study: Shimazu, Tadahiro, et al. "Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor." Science 339.6116 (2013): 211-214.

[00:21:42] HVMN.

[00:22:59] Epigenetic effects of ketones.

[00:27:27] BHB can affect vascular senescence; Study: Han, Young-min, et al. "β-Hydroxybutyrate prevents vascular senescence through hnRNP A1-mediated upregulation of Oct4." Molecular cell 71.6 (2018): 1064-1078.

[00:30:24] BHB inactivates the NLRP3 inflammasome; Study: Youm, Yun-Hee, et al. "The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome–mediated inflammatory disease." Nature medicine 21.3 (2015): 263.

[00:31:02] BHB protects against muscle protein wasting; Study: 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.

[00:32:11] Increased inflammatory response with ketone ester; Study: Neudorf, Helena, et al. "Oral Ketone Supplementation Acutely Increases Markers of NLRP3 Inflammasome Activation in Human Monocytes." Molecular nutrition & food research (2019): 1801171.

[00:35:52] Ketogenic diet and exogenous ketones reduce epileptiform spikes associated with Alzheimer’s: Newman, John C., et al. "Ketogenic diet or BHB improves epileptiform spikes, memory, survival in Alzheimer's model." bioRxiv (2017): 136226.

[00:36:51] Kenneth Ford, PhD.; Podcast: Optimal Diet and Movement for Healthspan, Amplified Intelligence and More with Ken Ford

[00:37:57] Cardiovascular effects of ketone infusions in humans; Studies: 1. Nielsen, Roni, et al. "Cardiovascular effects of treatment with the ketone body 3-hydroxybutyrate in chronic heart failure patients." Circulation 139.18 (2019): 2129-2141. 2. Gormsen, Lars C., et al. "Ketone Body Infusion With 3‐Hydroxybutyrate Reduces Myocardial Glucose Uptake and Increases Blood Flow in Humans: A Positron Emission Tomography Study." Journal of the American Heart Association 6.3 (2017): e005066.

[00:38:06] Ketone infusions in a paced model of cardiac failure in dogs. Study: Horton, Julie L., et al. "The failing heart utilizes 3-hydroxybutyrate as a metabolic stress defense." JCI insight 4.4 (2019).

[00:43:05] Ketogenic diet and gut health.

[00:44:31] Exogenous ketones affect stem cell regeneration and differentiation; Study: Cheng, Chia-Wei, et al. "Ketone Body Signaling Mediates Intestinal Stem Cell Homeostasis and Adaptation to Diet." Cell 178.5 (2019): 1115-1131. (We don’t have access to the Supplementary Methods, which contain Brianna’s favorite molecule!)

[00:46:02] Performance enhancing effects of lactate/propionate: Scheiman, Jonathan, et al. "Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism." Nature Medicine (2019): 1.

[00:47:22] Lucy Mailing; Podcast: How to Optimise Your Gut Microbiome.

[00:50:24] Improved performance with the ketone monoester; Study: Cox, Pete J., et al. "Nutritional ketosis alters fuel preference and thereby endurance performance in athletes." Cell metabolism 24.2 (2016): 256-268. 

[00:50:30] No performance benefit with ketone monoester supplement; Study: Evans, Mark, et al. "No Benefit of Ingestion of a Ketone Monoester Supplement on 10-km Running Performance." Medicine and science in sports and exercise 51.12 (2019): 2506-2515.

[00:52:00] Dr. Stephen Cunnane’s studies correlating blood ketone level and changing cognitive function and brain ketone uptake: Cunnane, Stephen C., et al. "Can ketones help rescue brain fuel supply in later life? Implications for cognitive health during aging and the treatment of Alzheimer’s disease." Frontiers in molecular neuroscience 9 (2016): 53; 2. Fortier, Mélanie, et al. "A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment." Alzheimer's & Dementia 15.5 (2019): 625-634.

[00:52:40] Breath ketone meters.

[00:57:03] Find Brianna on Twitter.