Ketone Esters a Smart Supplement? | Pure Nitrate vs. Beets | Caffeine Muscle Recruitment, Power and Performance

Time for a new installment of the supplement short news.
I think it's about time for another installment of the short news, i.e. an article that consists of several brief write-ups on very recent papers. Today's topics are: (1) the question whether it is a smart move to consume ketone esters on top of Gatorade or similar products before your workout; (2) the difference in physiological effects of potassium nitrate and beetroot juice; and (3) how caffeine improves muscle recruitment and hence endurance performance.
You can learn more about beetroot juice at the SuppVersity

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  • Ketone esters may be smart to consume on top of carbohydrate supplement before and during high-intensity exercise (Evans 2018) -- This is at least what you can assume based on the observations Evans & Egan made in their latest study.

    The researchers had N=11 male team sports athletes (mean±SD: age, 25.4±4.6 y; height 1.80±0.05 cm; body mass, 78.6±5.3 kg; VO2max 53.9±2.2 mL/kg/min) perform the same Loughborough Intermittent Shuttle Test (Part A, 5x15 min intermittent running; Part B, shuttle run to exhaustion) twice. Once with and once without extra 750 mg/kg of ketone esters (KE) in the 6.4% carbohydrate-electrolyte solution that was consumed before and during exercise.
    Figure 1: 15 m sprint times (A), and shuttle run time to exhaustion (B) during each trial. Data are presented as mean values, with error bars representing 95% confidence intervals (Evans 2018)
    In spite of the fact, that the provision of the supplement significantly increased plasma βHB concentrations from ~1.5 to 2.6 mM during exercise (P < 0.001), and notwithstanding the fact that plasma glucose and lactate concentrations were lower during KE compared to PLA (moderate-to-large effect sizes), neither the heart rate (HR), rate of perceived exertion (RPE), or 15 m sprint times differed significantly between trials. In fact, even "the run time to exhaustion was not different (P = 0.126, d = 0.45) between PLA [(mean (95% CI); 268, (199, 336) sec] and KE (229, (178, 280) sec]" (Evans 2018).

    What did differ - and that may actually surprise you, were the number of incorrect responses in a multi-tasking test increased from pre- to post-exercise in PLA [1.8 (−0.6, 4.1)] but not KE [0.0 (−1.8, 1.8)] (P = 0.017; d = 0.70) - an observation about which the scientists write:
    "The primary physiological role of ketogenesis as a survival mechanism during low carbohydrate availability is providing a substrate to the brain in the presence of diminishing blood glucose concentrations. Cognitive benefits and a neuroprotective role are established for exogenous ketones in non-exercise contexts. Notably, in a short-term (5 day) feeding study, rats supplemented daily with KME were 38% faster at completing a radial maze task, and made more correct decisions before making a mistake during the test" (Evans 2018).
    An issue the scientists still have to solve, though, is that several participants experienced incidences of GI symptoms. Hence, future studies should evaluate the dose-response effect in order to minimize both, dosing and GI stress in athletes.
  • NO-ergogenic? Beetroot juice works, pure potassium nitrate doesn't! (Thompson 2018) -- In their latest paper Christopher Thompson et al. describe an important experiment. While previous studies on different nitrate sources always focused on the acute effects of the intervention, the scientists from the Sport and Health Sciences Department at the University of Exeter, evaluated "the physiological and exercise performance adaptations to sprint interval training (SIT)" (Thompson 2018) in a 4-week study.
    Figure 2: Results of new meta-analysis of studies investigating the effect of nitrate (both from juice and supplements) on exercise performance; top - trained individuals vs. bottom untrained individuals - the comparison shows: trained subjects benefit less, mechanism probably anti-fatigue effect (Van de Walle 2018)
    To test if different types of NO3− supplementation evoke divergent physiological and performance adaptations to SIT, the authors compared the effects of 4-wk SIT with and without concurrent dietary NO3− supplementation administered as either NO3−-rich beetroot juice (BR) or potassium NO3− (KNO3) - and here's what they observed in their thirty recreationally active subjects
    • During severe-intensity exercise, V̇o2peak and time to task failure were improved to a greater extent with SIT + BR than SIT and SIT + KNO3 (P < 0.05).
    • There was also a greater reduction in the accumulation of muscle lactate at 3 min of severe-intensity exercise in SIT + BR compared with SIT + KNO3 (P < 0.05).
    • Plasma NO2− concentration fell to a greater extent during severe-intensity exercise in SIT + BR compared with SIT and SIT + KNO3 (P < 0.05).
    • There were no differences between groups in the reduction in the muscle phosphocreatine recovery time constant from pre- to postintervention (P > 0.05).
    The scientists believe that this result is a direct consequence of "greater NO-mediated signaling in SIT + BR compared with SIT + KNO3" (Thompson 2018) - an assumption that seems somewhat unlikely, the NO2- levels did, after all, plummet faster in the beetroot vs. control and KNO3 groups. Accordingly, one may at least speculate that the ergogenic effects depend on other substances in the beetroot juice, such as betalain which has a track record of significantly improving athletic performance (Van Hoorebeke 2016; Montenegro 2016).
  • More activity = higher performance - Caffeine's performance benefits may indeed be, at least partially, mediated by increased "muscle recruitment, which enables greater work done above critical power and a greater degree of end-exercise decline in quadriceps twitch force during a 4-km cycling time trial" (Felippe 2018).

    Now, what is interesting is that this result of a recent study on the influence of caffeine on the total work done above critical power (CP) during a 4-km cycling time trial (TT) and the subsequent consequence on the development of central and peripheral fatigue is that the improvements come at a cost in form of greater locomotor muscle fatigue. 
  • In the study, nine cyclists had performed three constant-load exercise trials to determine CP and two 4-km TTs ~75 min after oral caffeine (5 mg/kg) or cellulose (placebo) ingestion. Neuromuscular functions were assessed before and 50 min after supplementation and 1 min after TT. Oral supplementation alone had no effect on neuromuscular function (P > 0.05). Compared with placebo, caffeine increased mean power output (~4%, P = 0.01) and muscle recruitment (as inferred by EMG, ~17%, P = 0.01) and reduced the time to complete the TT (~2%, P = 0.01). Work performed above CP during the caffeine trial (16.7 ± 2.1 kJ) was significantly higher than during the placebo (14.7 ± 2.1 kJ, P = 0.01). End-exercise decline in quadriceps twitch force (pre- to postexercise decrease in twitch force at 1 and 10 Hz) was more pronounced after caffeine compared with placebo (121 ± 13 and 137 ± 14 N vs. 146 ± 13 and 156 ± 11 N; P < 0.05). There was no effect of caffeine on central fatigue. 
When timing seems to matter: "Protein-Timing & Fasting: Fasted Sprints & the Remarkable Muscle↑, Fat↓ Effect of Timing Whey With vs. Between Meals" (read it)
So what's the verdict then? (A) Keep drinking your pre-workout coffee, unless you have a gene-test showing that you are a slow metabolizer and feel no performance increase or even a decrement when taking caffeine before workouts. (B) No matter what your source may be: nitrates are currently a hype supplement but the effect size is small, relevant mostly for untrained individuals and probably significantly more pronounced in its natural form, i.e. from beetroot juice vs. potassium nitrate. (C) For your muscles the extra-ketones you may be consuming alongside your Gatorade may be overkill (hence no performance benefits), but your brain may thank you for the extra fuel | Comment!
References:
  • Evans, Mark & Egan, Brendan. "Intermittent Running and Cognitive Performance after Ketone Ester Ingestion." Medicine & Science in Sports & Exercise: June 25, 2018 - Publish Ahead of Print
  • Leandro Camati Felippe, Guilherme Assunção Ferreira, Sara Kely Learsi, Daniel Boari, Romulo Bertuzzi, and Adriano Eduardo Lima-Silva. "Caffeine increases both total work performed above critical power and peripheral fatigue during a 4-km cycling time trial." Journal of Applied Physiology 2018 124:6, 1491-1501.
  • Christopher Thompson, Anni Vanhatalo, Stefan Kadach, Lee J. Wylie, Jonathan Fulford, Scott K. Ferguson, Jamie R. Blackwell, Stephen J. Bailey, and Andrew M. Jones. "Discrete physiological effects of beetroot juice and potassium nitrate supplementation following 4-wk sprint interval training." Journal of Applied Physiology 2018 124:6, 1519-1528.
  • Montenegro, Cristhian F., et al. "Betalain-rich concentrate supplementation improves exercise performance and recovery in competitive triathletes." Applied Physiology, Nutrition, and Metabolism 42.2 (2016): 166-172.
  • Van De Walle, Gavin P., and Matthew D. Vukovich. "The Effect of Nitrate Supplementation on Exercise Tolerance and Performance: A Systematic Review and Meta-Analysis." The Journal of Strength & Conditioning Research 32.6 (2018): 1796-1808.
  • Van Hoorebeke, Justin S., et al. "Betalain-rich concentrate supplementation improves exercise performance in competitive runners." Sports 4.3 (2016): 40.
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