Effects of dietary nitrate on skeletal muscle energetics and exercise performance

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1 Effects of dietary nitrate on skeletal muscle energetics and exercise performance Anni Vanhatalo PhD Sport and Health Sciences University of Exeter, UK

2 Nitric Oxide Neurotransmission Ca 2+ Handling Glucose Uptake Vasodilation Mitochondrial Respiration Muscle Force Production

3 Pathways of NO synthesis Nitrate NO 3 - L-arginine + O 2 Bacterial NO 3 - reductases Deoxy Hb, Mb Respiratory enzymes XOR enos Carbonic anhydrase Vitamin C Polyphenols Nitrite NO 2 - NO NOS

4 Exercise economy / efficiency Larsen et al. Acta Physiol 2007 * 3-5 % Larsen et al. (2007): 3 days supplementation with 0.1 mmol/kg/day NaNO 3 -

5 Good sources of nitrate Source mg/100g Carrot Lettuce Spinach Chinese cabbage Bok choy Cabbage Cole Rocket (Arugula) Rhubarb 281 Beetroot 110 Good sources of nitrate (mg/100g).

6 Beetroot Juice We wished to investigate whether: 1) Similar effects to those of Larsen et al. (2007) were manifest following dietary supplementation with nitrate-rich beetroot juice 2) The potential improvement in exercise economy might enhance exercise tolerance Bailey et al., 2009, J Appl Physiol

7 Effects of BR on Plasma [NO 2- ] and Blood Pressure Mean Plasma [NO 2 - ] (nm) * Placebo Nitrate 134 Mean Systolic BP (mmhg) Placebo * Nitrate * P < 0.05

8 Influence of Nitrate on O 2 Cost of Moderate Exercise 1600 Pulmonary VO 2 (ml min -1 ) PLACEBO NITRATE Time (s)

9 Influence of Nitrate on Exercise Tolerance VO 2 (% Primary Amplitude) PLACEBO 0 NITRATE Time (s) Time-to-Exhaustion (s) * 16 % * = P < 0.05 Placebo Nitrate

10 5 min 5 min 90% GET 10 min rest 90% GET 10 min rest 30 W.min -1 Ramp incremental test

11 Influence of Dietary Nitrate Supplementation on Cycling Economy VO 2 (L.min -1 ) Placebo Baseline Placebo 2.5 h post Placebo 5 days Placebo 15 days Time (s) Time (s) Time (s) VO 2 (L.min -1 ) Nitrate Baseline Nitrate 2.5 h post Nitrate 5 days Nitrate 15 days Time (s) Vanhatalo et al. (2010) Am J Physiol Time (s) Time (s)

12 Ramp incremental exercise:. peak work rate and VO 2 max Baseline Placebo Nitrate 360 * # 3.8 * Peak work rate (W) VO 2 max (L.min -1 ) BL 2.5 h 5 d 15 d 0.0 BL 2.5 h 5 d 15 d * Different from baseline; # Different from Placebo; P < 0.05 * P < 0.001

13 End-Exercise VO 2 (L.min -1 ) % 3.0 % * * PL 70 ml BR PL 140 ml BR PL 280 ml BR

14 Exercise tolerance: the dose-response relationship % * % * Time-to-Exhaustion (s) * Significantly different from PL (P < 0.05) PL BR PL BR PL BR 70 ml 140 ml 280 ml

15 Mechanisms Six day supplementation with: Beetroot (NO 3 - = 5.1 mmol day -1 ) and Placebo (NO 3 - = negligible) Days 4 & 5 Power Output (W) Laboratory- Pulmonary VO 2 LOW LOW HIGH T lim Bailey et al., 2010, J Appl Physiol Power Output (W) Day 6 Time (Min) HIGH 31 P MRS- Muscle Energetics LOW LOW T lim Time (Min)

Influence of Dietary Nitrate on VO 2 and

1600 1400 1200 1000 800 600 400 +25% 0 300

[PCr] (mm) 30 25 20 15 Placebo Nitrate # #

16 Influence of Dietary Nitrate on VO 2 and Muscle [PCr] Dynamics VO 2 (ml min -1 ) % # [PCr] (mm) Placebo Nitrate # # P< Time (s)

17 Mechanisms: nitrate and mitochondria Larsen et al. (2011). Cell Metabolism, 13,

18 38% 50%

19 Blood flow and vascular conductance (cont.) Targeted effects of NO 3 - Glycolytic Oxidative

20 Oxidation NO 3 - NO 2 - NO Reduction

21 Muscle metabolic perturbation 5 0 [PCr] Normoxia Hypoxia PL Hypoxia BR Δ [PCr] (mm) * Time (s) * T lim different from CON and H-BR (P<0.05)

22 Muscle metabolic perturbation [ph] Normoxia Hypoxia PL Hypoxia BR Δ ph Time (s) * * T lim different from CON and H-BR (P<0.05)

23 Implications Disease conditions in which muscle O 2 delivery is impaired High altitude exposure High-intensity exercise

24 Effects of nitrate on exercise tolerance Constant work-rate exercise Incremental exercise ~5% Tlim CWR Tlim Increm ental ~15% Bailey et al. (2009) 70%d Bailey et al. (2010) knee-ext. Lansley et al. (2011a) running Vanhatalo et al. (2010) after 2.5 h Vanhatalo et al. (2010) after 5 d Vanhatalo et al (2011) hypoxia Kelly et al. (2013) 100%VO2max Kelly et al. (2013) 80%Δ Vanhatalo et al. (2010) after 15 d Lansley et al. (2011a) knee-ext. Kelly et al. (2013) 70%Δ Kelly et al. (2013) 60%Δ Wylie et al. (2013b) 4 shots Kenjale et al. (2011) PAD Masschelein et al. (2012) Hypoxia Wylie et al. (2013b) 2 shots Bescos et al. (2011) Wylie et al. (2013b) 1 shot Thompson et al. (unpub)? Larsen et al (2010) Change in T lim (%) Change in T lim (%)

25 How about time-trial performance? Lansley et al. (2011b) untrained, acute Lansley et al. (2011b) untrained, acute Murphy et al. (2012) untrained, acute Wilkerson et al. (2012) trained, acute Peacock et al. (2012) trained, acute Bescos et al. (2012) trained, 3 d ~1.2% Cermak et al. (2012b) trained, acute Cermak et al. (2012a) untrained, 6 d Muggeridge et al. (2013b) trained, acute, hypoxia Muggeridge et al. (2013a) trained, acute Christensen et al. (2013) trained, 6 d Change in performance (%)

26 The Effect of Nitrate Supplementation on Exercise Performance in Healthy Individuals: A Systematic Review and Meta-Analysis Across studies measuring time trial performance in trained cohorts, there was a ~0.9% improvement following nitrate supplementation. To put this in context, the measured difference between first and fourth place for elite swimming performance has been calculated to be 0.6% (Trewin et al., 2004), and improvements as little as 0.3% have been noted to be valuable to elite track and field athletes (Hopkins, 2005). Hoon et al., Int J Sport Nutr Exer Metab 2013

27 Elite sports performance

28 Nitrate supplementation in elite athletes Reasons why nitrate may be less effective in highlytrained endurance athletes: Higher NOS activity Higher baseline plasma [nitrite] Better muscle oxygenation Higher mitochondrial volume and efficiency Higher proportion of type I fibres Majority of studies with highly-trained endurance athletes have used acute supplementation of ~4-8 mmol nitrate.

(rowing/kayaking/cycling/running) Exercise intensity/duration/type (2-40

duration) The individual (responders vs.

29 Is nitrate ergogenic in the elite? It depends on a complex combination of factors: Type of sport/event (rowing/kayaking/cycling/running) Exercise intensity/duration/type (2-40 min?; continuous or intermittent) Supplementation procedures (dose and duration) The individual (responders vs. non-responders) Aerobic fitness/training status (effects less likely when VO 2 max >70-75 ml/kg/min) - might still be useful in 99.9% of the population.

30 With thanks... Andy Jones Jamie Blackwell Stephen Bailey Jimmy Kelly Fred DiMenna Lee Wylie Paul Winyard Jon Fulford

Dietary Nitrate Supplementation Enhances Maximal Oxygen Consumption of well-trained Male Athletes

Original article: Dietary Nitrate Supplementation Enhances Maximal Oxygen Consumption of well-trained Male Athletes Dr. DileepTirkey* Assistant Professor, Lakshmibai National Institute of Physical Education,