There’s been a number of studies and inferences for consuming exogenous ketones (i.e. consumed vs. produced by the body) as a way to improve endurance sports performance.
While the jury’s still sitting, and the verdict still coming on ketones and performance, there seems to be more progressive consistent evidence on the role of exogenous ketones and amino acids in improved protein sparing and muscle recovery.
Early findings of the 70s
In the mid-70s, studies and papers were being published on the potential of ketone infusions, and their effect on reduced nitrogen excretion from the body. These studies were already poking at the question of nitrogen balance, and whether ketones (namely, beta-hydroxybutyrate, or B-OHB) could reduce the oxidation of protein (amino acids) and the excretion of nitrogen. Studies on extended fasts showed how B-OHB reduced plasma levels of alanine (upto 48%) in a protein sparing-like effect, with notable reduction in urinary nitrogen excretion.
Interesting note in these early studies was reference to glutamine – and that typically during catabolic (fasting) states glutamine levels decrease. We now know from other papers, several decades later, that extended endurance exercise training (an effective caloric equivalent of fasting) causes measurable reduction in glutamine levels, and this alone could be used as a potential marker of over-training.
More Insight from the 80's
In the mid-80s further studies looked at the effect of B-OHB on sparing of specific amino acids, and human skeletal muscle synthesis. Various amino acids were studied, across researchers in evaluating the protein-sparing effects of B-OHB. Leucine is commonly used in studies as a marker of protein turnover, in light of its signaling and triggering role in protein synthesis. This doesn’t mean that leucine (or for that matter any specific Brach Chain Amino Acid) alone is sufficient for muscle recovery and nutrition. In particular, some studies at this time showed how the infusion of B-OHB reduced the oxidation of leucine by upto 41% with a mean impact of 30%. Further to this researchers noted an increase of leucine incorporation into skeletal muscle protein of 5-17%, with a mean of 10%, through B-OHB infusions.
More recently –
Besides various animal studies highlighting similar protein synthesis improvements of B-OHB intake, researchers began to also look at oral consumption (drink) of ketones in promoting muscle synthesis. In a double-blind study, a maltodextrin drink and a Ketone drink (Ketone esters) was given to subjects. The study showed an enhanced activation of a key protein complex in the body called mTOR1, responsible for protein synthesis, and protein activation. While Ketone Esters receive a consistent bad wrap on taste and price, industry shifted sport-nutrition drink formulations to include a sodium B-OHB powder, which has next to zero taste.
B-OHB and Amino Acids, Lab and field findings.
As at 2020, The World Anti-Doping Agency (WADA) didn’t see sufficient evidence for inclusion of Ketones in any of its forms to be included on the prohibited substance list for athletes. As mentioned earlier – the jury is still out on the direct effect, if any, of exogenous ketones for enhanced performance.
The more interesting application, may be in accelerated muscle recovery thereby charting a path for consistently high-intensity or volume training blocks in preparation for targeted seasonal competitions and A-races.
Stepping out of the clinical constraints of laboratory testing, 100 mile world record holder on track and treadmill, Zach Bitter began using a higher-dose recovery formulation, including B-OHB as part of his volume ramp for his upcoming 24hour race.
This would be Bitters first primary focus 24-hour build up, where his training has been focused specifically on the pacing and structure for 24-hours. At the height of his core-training blocks, at 2-5weeks out from race day, Bitter had been absorbing mega-volume weeks of over 200miles and in his perspective ‘hadn’t really felt beat-up at all’.
Bitter, would consume incremental protein in food, bars and shakes (with B-OHB and Glutamine), notably in the morning in looking to break the period between the prior evening meal, and his morning run.
Bitter said, “raising quality protein intakes is important in these high-volume ramps you your A-races, and spacing the intake of protein across each day helps mitigate periods of potential catabolism, or breakdown of muscle tissue – which you want to try and avoid.”
With eccentric muscle contractions (like the running movement), being a well published causative factor in muscle damage, delayed muscle soreness and risk-factor to consistent high quality training blocks, much interest is in nutrition and soft-tissue work that can minimize muscle tissue damage.
Whey protein isolate has been studied multiple times in evaluating its effects on resistance training, but only more recently it’s role in supporting recovery from aerobic eccentric muscle contraction activities, like endurance running. In 2017, a study looked at post-day Marathon, and 1-week post marathon, blood muscle-damage markers and 1-week post-marathon performance test of elite athletes. Athletes were provided either Whey protein, or a placebo-maltodextrin based formula for 5 weeks of supplementation prior to the marathon and tests. The studied showed notably lower muscle-damage blood markers in the Whey group, performance of the whey group was consistently superior in the 1-week post marathon performance test.
Additional studies have narrowed in on specific amino acids, like leucine, which are highest in whey protein, and also mixed formulations of leucine and glutamine. These studies also looked at muscle-damage blood markers and athletes scores on recovery from delayed soreness – and likewise reported lower blood markers of muscle damage-inflammation, and reduced soreness.
Separate to the muscle-damaging effects of eccentric exercise, exercise induced heat-stress is also an increasing research area (on animals and humans), in respect to its effect on muscle damage and gut-membrane damage.
Most notably, Glutamine has received consistent attention in its anti-inflammatory and protective effect against exercise induced heat-stress to muscle tissue, immune-competence, and the integrity of the gut membrane. While on-going research continues to investigate the implications of exercise triggered leakage of highly-inflammatory toxins (endotoxins) into the systemic circulation, Glutamine is showing to be a positive nutritional to help mitigate the risk.
Bringing it all together
This evolving research was the genesis of SFuels development team its professional athletes and science staff formulating the SFuels REVIVAL formulation built on Whey protein, Sodium B-OHB and Glutamine. The unique formulation also includes C8 Medium Chain Triglycerides and collagen, while avoiding the use of any sugars, maltodextrin and sugar alcohols. Results and feedback has been impressive, both in training, racing and most notable its great taste (chocolate).
All the best in accelerating your recovery, and elevating your training volumes to hit your next A-Race at your optimum performance.
Go Longer. Team SFuels.
- Effect of ketone infusions on amino acid and nitrogen metabolism in man. R S Sherwin, R G Hendler, and P Felig. J Clin Invest. 1975 Jun; 55(6): 1382–1390.
- Effect of beta-hydroxybutyrate on whole-body leucine kinetics and fractional mixed skeletal muscle protein synthesis in humans. K S Nair, S L Welle, D Halliday, and R G Campbell. The journal of Clinical Investigation. July 1988.
- Branched-Chain Amino Acids (Leucine, Isoleucine, and Valine) and Skeletal Muscle. Stefan H.M. Gorissen Stuart M.Phillips. 2019. https://www.sciencedirect.com/science/article/pii/B9780128104224000166
- The Emerging Role of Glutamine as an Indicator of Exercise Stress and Overtraining. David G. Rowbottom, David Keast & Alan R. Morton. Sports Medicine volume 21, pages80–97(1996).
- Comparative effects of whey protein versus L-leucine on skeletal muscle protein synthesis and markers of ribosome biogenesis following resistance exercise. C. Brooks Mobley et al. Amino Acids volume 48, pages733–750(2016)
- The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization in mice. Jae-Sung You, Garrett B. Anderson, Matthew S. Dooley, Troy A. Hornberger. Dis Model Mech. 2015 Sep 1; 8(9): 1059–1069.
- Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. S C Bodine et al. Nat Cell Biol 2001 Nov;3(11):1014-9. doi: 10.1038/ncb1101-1014.
- Whey Protein Improves Marathon-Induced Injury and Exercise Performance in Elite Track Runners. Wen-Ching Huang et al. Int J Med Sci. 2017; 14(7): 648–654.
- The effects of acute leucine or leucine-glutamine co-ingestion on recovery from eccentrically biased exercise. Mark Waldron et al. Amino Acids. 2018 Jul;50(7):831-839. doi: 10.1007/s00726-018-2565-z.
- Glutamine improves heat stress-induced oxidative damage in the broiler thigh muscle by activating the nuclear factor erythroid 2-related 2/Kelch-like ECH-associated protein 1 signaling pathway. Hong Hu, Sifa Dai, Jiaqi Li, Aiyou Wen, Xi Bai. Poult Sci . 2020 Mar;99(3):1454-1461. doi: 10.1016/j.psj.2019.11.001.
- Determination of the anti-inflammatory and cytoprotective effects of l-glutamine and l-alanine, or dipeptide, supplementation in rats submitted to resistance exercise. Raquel Raizel et al. Br J Nutr. 2016 Aug;116(3):470-9. doi: 10.1017/S0007114516001999.
- Heat stress, gastrointestinal permeability and interleukin-6 signaling — Implications for exercise performance and fatigue. Nicole Vargas, Frank Marino. Temperature (Austin). 2016 Apr-Jun; 3(2): 240–251.
- Systematic review: exercise‐induced gastrointestinal syndrome—implications for health and intestinal disease. R. J. S. Costa R. M. J. Snipe C. M. Kitic P. R. Gibson. Alimentary Pharmacology and Therapeutics. June 2017
- Glutamine Supplementation In Vitro and In Vivo, in Exercise and in Immunodepression. Linda M. Castell. Sports Medicine volume 33, pages323–345(2003).