Effects of dietary nitrate on skeletal muscle energetics and exercise performance Anni Vanhatalo PhD Sport and Health Sciences University of Exeter, UK
Nitric Oxide Neurotransmission Ca 2+ Handling Glucose Uptake Vasodilation Mitochondrial Respiration Muscle Force Production
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
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 -
Good sources of nitrate Source mg/100g Carrot 92-195 Lettuce 12-267 Spinach 24-741 Chinese cabbage 43-161 Bok choy 102-310 Cabbage 26-125 Cole 77-137 Rocket (Arugula) 300-329 Rhubarb 281 Beetroot 110 Good sources of nitrate (mg/100g).
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
Effects of BR on Plasma [NO 2- ] and Blood Pressure Mean Plasma [NO 2 - ] (nm) 350 250 150 50 * Placebo Nitrate 134 Mean Systolic BP (mmhg) 132 130 128 126 124 122 Placebo * Nitrate * P < 0.05
Influence of Nitrate on O 2 Cost of Moderate Exercise 1600 Pulmonary VO 2 (ml min -1 ) 1400 1200 1000 PLACEBO NITRATE -60 0 60 120 180 240 300 360 Time (s)
Influence of Nitrate on Exercise Tolerance VO 2 (% Primary Amplitude) 160 140 120 100 80 60 40 20 PLACEBO 0 NITRATE -60 0 60 120 180 240 300 360 420 480 540 600 1000 Time (s) Time-to-Exhaustion (s) 800 600 * 16 % * = P < 0.05 Placebo Nitrate
5 min 5 min 90% GET 10 min rest 90% GET 10 min rest 30 W.min -1 Ramp incremental test
Influence of Dietary Nitrate Supplementation on Cycling Economy 1.5 1.4 1.3 VO 2 (L.min -1 ). 1.2 1.1 1.0 0.9 0.8 Placebo Baseline Placebo 2.5 h post Placebo 5 days Placebo 15 days 0.7-60 0 60 120 180 240 300 1.5 Time (s) 1.4-60 0 60 120 180 240 300 Time (s) -60 0 60 120 180 240 300 Time (s) VO 2 (L.min -1 ). 1.3 1.2 1.1 1.0 0.9 0.8 Nitrate Baseline Nitrate 2.5 h post Nitrate 5 days Nitrate 15 days 0.7-60 0 60 120 180 240 300 Time (s) Vanhatalo et al. (2010) Am J Physiol -60 0 60 120 180 240 300 Time (s) -60 0 60 120 180 240 300 Time (s)
Ramp incremental exercise:. peak work rate and VO 2 max Baseline Placebo Nitrate 360 * # 3.8 * Peak work rate (W) 340 320 300 VO 2 max (L.min -1 ). 3.6 3.4 3.2 3.0 0 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
End-Exercise VO 2 (L.min -1 ). 1.75 1.70 1.65 1.60 1.5 5 1.8 % 3.0 % * * 0.0 0 PL 70 ml BR PL 140 ml BR PL 280 ml BR
Exercise tolerance: the dose-response relationship 650 14.5 % * 600 12.0 % * Time-to-Exhaustion (s) 550 500 450 0 * Significantly different from PL (P < 0.05) PL BR PL BR PL BR 70 ml 140 ml 280 ml
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) 0 3 6 9 12 15 18 21 24 27 30 Day 6 Time (Min) HIGH 31 P MRS- Muscle Energetics LOW LOW T lim 0 3 6 9 12 15 18 21 24 27 30 Time (Min)
Influence of Dietary Nitrate on VO 2 and Muscle [PCr] Dynamics VO 2 (ml min -1 ) 1800 1600 1400 1200 1000 800 600 400 +25% 0 300 600 900 1200 1500 1800 2100 2400 # 40 35 [PCr] (mm) 30 25 20 15 Placebo Nitrate # # P<0.01 0 300 600 900 1200 1500 1800 2100 2400 Time (s)
Mechanisms: nitrate and mitochondria Larsen et al. (2011). Cell Metabolism, 13, 149-159
38% 50%
Blood flow and vascular conductance (cont.) Targeted effects of NO 3 - Glycolytic Oxidative
Oxidation NO 3 - NO 2 - NO Reduction
Muscle metabolic perturbation 5 0 [PCr] Normoxia Hypoxia PL Hypoxia BR Δ [PCr] (mm) -5-10 -15-20 * -25 0 120 240 360 480 600 Time (s) * T lim different from CON and H-BR (P<0.05)
Muscle metabolic perturbation 0.15 0.10 0.05 0.00 [ph] Normoxia Hypoxia PL Hypoxia BR Δ ph -0.05-0.10-0.15-0.20-0.25 0 120 240 360 480 600 Time (s) * * T lim different from CON and H-BR (P<0.05)
Implications Disease conditions in which muscle O 2 delivery is impaired High altitude exposure High-intensity exercise
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) 0 5 10 15 20 25 30 Change in T lim (%) 0 5 10 15 20 Change in T lim (%)
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 -1 0 1 2 3 4 Change in performance (%)
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
Elite sports performance
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.
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.
With thanks... Andy Jones Jamie Blackwell Stephen Bailey Jimmy Kelly Fred DiMenna Lee Wylie Paul Winyard Jon Fulford