05 June 2014

Coffee, caffeine and mountain ultramarathon running

There are some moments in life that will stay with you forever. I never thought that drinking a cup of coffee would be one of those moments. Now I can just close my eyes to still smell and taste the exact flavor of the cup of coffee I had around 11 in the morning on September 12 last year. I remember that the coffee was slightly too strong and that the beans were too dark and that they were roasted too long for my normal taste. But, it is still the best cup I have ever tasted. It made me wake up from the bad disoriented nightmare I was having. I suddenly found myself looking out over the beautiful valley of Valpelline with the river Le Buthier far below me and the sun radiantly shining in the clear blue sky above Mont Faceballa.  I was standing just a few vertical hundred meters from Col Brison the last day of my Tor des Géants adventure and had been racing for close to 100 hours and 276 kilometers.

Col Brison towards the end of Tor des Géants in the Aosta Valley in Italy
Obviously, I knew about the effects of caffeine before, being a habitual coffee and tea drinker, but I had never experienced the powerful effects it could have during a mountain ultramarathon trail race as I did at that moment. Without this cup I am not even sure I would have literaly survived that morning, I was so disoriented due to sleep deprivation and even though the ascent was, comparably, not that strenuous, the following ascent down to Ollomont and the last life base was really though and one of the steepest during the race where a fall could have been disastrous. The coffee enabled me to not only wake up with enhanced mental focus and continue the race safely, but also increase my speed considerably. Now in planning for Petite Trotte à Léon (PTL) I know that caffeine in the form of both coffee and in gels will be an extremely important aid for us to make it. However, I became interested in seeing if my anecdotal experience of coffee as increasing my performance has been proven for running in scientific studies.

Caffeine is probably the most widely used drug as about 90% of adults consume it in their daily eating and drinking patterns. The ergogenic (work-enhancing) effects of caffeine in reducing fatigue and increasing wakefulness and alertness have been recognised for many centuries (Burke “Caffeine and sport performance” Appl Physiol Nutr Metab 2008; http://en.wikipedia.org/wiki/Coffee). Caffeine is a methylxanthine (xanthine alkaloid) that blocks adenosine receptors, has actions on essentially all human tissues and readily pass the blood-brain-barrier The serum concentration of caffeine peak 15 to 120 min after ingestion, with a half-life ranging from 2.5 to 6 h and it has effects persisting for up to 6 h or more after ingestion (Arnaud “The pharmacology of caffeine” Prog Drug Res 1987; 31: 273-313; http://en.wikipedia.org/wiki/Caffeine).

The predominant mechanisms of the ergogenic benefits of caffeine are still unknown. However, a number of possible mechanisms of action have been proposed (reviewed in Graham “Caffeine and Exercise – Metabolism, Endurance and Performance” Sprots Med 2001; 31: 785-807; Burke “Caffeine and sport performance” Appl Physiol Nutr Metab 2008; 33: 1319–1334; Tarnopolsky “Effect of caffeine on the neuromuscular system – potential as an ergogenic aid Appl Physiol Nutr Metab 2008; 33: 1284 -1289; Goldtstein et al “International society of sports nutrition position stand: caffeine and performance” J Int Soc Sports Nutr 2010; 7:5; Getzin et al “Nutrition update for the ultraendurance athlete” Curr Sports Med Rep 2011; 10: 330-339; Pesta et al “The effects of caffeine, nicotine, ethanol and tetrahydrocannabinol on exercise performance” Nutr Metab 2013; 10:71):

1)      inhibition of phosphodiesterase and glycogen phosphorylase with a subsequent increase in fat oxidation/lipolysis and preservation of glycogen;
2)      mobilization of intracellular calcium via release from the sarcoplasmic reticulum, which improves muscle contractility;
3)      antagonism of central adenosine receptors;
4)      increase in b-endorphin and cortisol release, which may alter the athlete’s perception of pain and fatigue)

A fifth possibility is a placebo/nocebo effect on pain. It is interesting that the effects of caffeine are more pronounced in painful high-intensity endurance sports, like cycling and running, compared to short duration interactive stop-go sports, like team and racquet sports [i.e tennis in most studies]  (Beedie “All in the mind? Pain, placebo effect, and ergogenic effect of caffeine in sports performance” Open Access Journal of Sports Medicine 2010: 1: 87–94).

Mechanisms behind the effects of coffee on sports performance. From Burke 2008.
While 3 to 6 mg x kg–1 caffeine may be beneficial, higher doses may be more harmful than helpful. Common side effects of caffeine include nausea, stool urgency and frequency, diarrhea, jitteriness, palpitations, anxiety, tachycardia, elevated blood pressure, headaches, insomnia, physiologic addiction, and withdrawal symptoms. Caffeine consumption over 15 mg x kg–1 can cause headaches and more profound nervousness, and 200 mg x kg–1 can invoke seizures and death.

During recent years there have been numerous studies conducted on the effect of caffeine on sports performance and good recent reviews have been published (Keisler & Armsey  “Caffeine as an ergogenic aid” Curr Sports Med Rep 2006; 5: 215-219; Burke “Caffeine and sport performance” Appl Physiol Nutr Metab. 2008; 33:1319–1334; Jones G “Caffeine and other sympathomimetic stimulants: modes of action and effects on sports performance” Essays Biochem. 2008; 44: 109-123; Ganio  et al “Effect of caffeine on sport-specific endurance performance: a systematic review” J Strength Condition Res 2009; 23: 315-24; Goldtstein et al “International society of sports nutrition position stand: caffeine and performance” J Int Soc Sports Nutr 2010; 7:5). The beneficial ergogenic effects of caffeine has been shown to be more evident in endurance and sustained high-intensity closed skill sports, like cycling, rowing and middle-distance running,  than in interactive and stop-go sports as mentioned above. The ergogenic effects of caffeine can be obtained at doses at or below the daily intake of normal populations and below levels representing health risks. Caffeine is despite the ergogenic effects therefore not currently proscribed by the World Anti-Doping Agency.

Reading the literature on caffeine and sports performance enhancement I was surprised to see that there are not many studies performed in running at all and that most studies done have been time-to-exhaustion trials on a treadmill rather than a time trial over a fixed distance simulating the race settings. And, not surprisingly, there have been no studies performed at all on the effect of caffeine in ultramarathons and mountain trail running. I will anyway below review all studies I have found of caffeine and running for distances longer than 5 kilometers. I have included some studies on energy drinks, despite the fact that they might contain other active ingredients, including carbohydrates, than caffeine (reviewed in Campbell et al “International Society of Sports Nutrition position stand: energy drinks” J Int Soc Sport Nutr 2013; 10:1).

Previous reviews and meta-analysis of studies looking at whether caffeine improves running performance have found small to moderate effects of 0.9% (Ganio  et al “Effect of caffeine on sport-specific endurance performance: a systematic review” J Strength Condition Res 2009; 23: 315-24), 1.1% (Schubert & Astorino “A systematic review of the efficacy of ergogenic aids for improving running performance” J Strength Cond Res 2013; 27: 1699-1707). This is low compared to the effects seen in most cycling trials of around 4%. In cycling it has also been shown in a systematic meta-analysis that addition of caffeine to carbohydrate supplementation lead to an improvement, see figure below (Conger et al “Does caffeine added to carbohydrate provide additional ergogenic benefit for endurance” Int J Sport Nutr Exerc Metab 2011; 21: 71-84).
 
From Conger et al 2011
Also in several studies on muscular strength and endurance caffeine has been shown to have beneficial effects , in particular in studies of the knee extensors, see figures below (Warren et al “Effect of caffeine ingestion on muscular strength and endurance: A meta-analysis” Med Sci Sports Exerc 2010; 42: 1375-1387).
 




Looking at the results in the studies below it is clear that despite the fact that most studies have been well-performed in a cross-over double-blind design they are all very small and almost none use relevant endpoints for running. And, rather surprisingly, most studies fail to show beneficial performance enhancing effects contrary to what I had believed before starting the search.

 
High intensity time-to-exhaustion and timed treadmill running trials

Cadarette et al “Effects of varied dosages of caffeine on endurance exercise to fatigue” in Biochemistry of Exercise, ed Knuttgen H. (Human Kinetics, Boston, MA), 1982: pp 871–877 (27% improvement?)
In this blinded cross-over study 8 trained athletes ran at 80% of VO2max until exhaustion after ingestion of placebo, 2.2, 4.4 or 8.8 mg x kg–1of caffeine. Endurance was improved from 53.4 min in the placebo group to 67.8 min in the 2.2 group and 73.4 min in the 4.4 group. There was no improvement in the highest 8.8 group (57.9 min). The study contained some weaknesses as there was one outlier in the 4.4 group that could explain the high value in this group. Furthermore, the concentration of caffeine in blood in the placebo group was equivalent to a dose of approximately 3 mg x kg–1.

McNaughton “The influence of caffeine on incremental treadmill running” Br J Sport Med 1986; 20: 109-112 (6% improvement)
In this double-blind cross-over study 12 male athletes normally participating in team-sports were running to exhaustion on a treadmill that first was set to 70-75% of VO2max ,followed by an increase in gradient and speed, after ingestion of a control, placebo, small (10 mg x kg–1) or large (15 mg x kg–1) caffeine dose. The mean time to exhaustion increased by 6% from 48 minutes 03 seconds in the placebo (decaffeinated) group to 50 minutes 52 seconds in the high-dose 15 mg x kg–1caffeine group (p < 0.05). There was no enhancement of performance with the lower caffeine dose.

Graham & Spriet “Performance and metabolic responses to a high caffeine dose during prolonged exercise” J Appl Physiol 1991; 71: 2292-2298 (31% improvement)
In this double-blind cross-over study 7 well-trained male runners performed a treadmill running trial of approximately 85% VO2max after either ingesting placebo or 9 mg x kg–1 caffeine. They found a marked and statistically significant enhancement of 31% the endurance time after ingestion of caffeine (caffeine 71.0 ± 11.0 min versus placebo 49.2 ± 7.2 min; p < 0.05).

French et al “Caffeine ingestion during exercise to exhaustion in elite distance runners” J Sports Med Phys Fitness 1991; 31: 425-432 (Significant improvement)
In this study six seasoned marathon runners were running to exhaustion on a treadmill after taken either nothing (control), placebo or caffeine 10 mg x kg–1 in a double-blind cross-over study. They ran first at 75% VO2max for 45 minutes, followed by an increase of speed by 2 miles per hour until exhaustion. Caffeine increased time to exhaustion significantly compared to placebo and control. One interesting finding in this study was that caffeine was taken immediately prior to exercise, in comparison to most other experiments where the drug was ingested 1-2 hours prior to exercise.

Graham & Spriet “Metabolic, catecholamine, and exercise performance responses to various doses of caffeine” J Appl Physiol 1995; 78: 867-74 (22% improvement)
In this double blind cross-over study three doses of caffeine 3, 6, or 9 mg x kg–1 and placebo were given to eight runners one hour before they ran to exhaustion at 85% of maximal VO2max. Plasma caffeine concentration increased with each dose, while the major metabolite, paraxanthine, did not increase between the 6 and 9 mg x kg–1 doses, suggesting that hepatic caffeine metabolism was saturated. Endurance was enhanced with both 3 and 6 mg x kg–1 of caffeine (increases of 22 +/- 9 and 22 +/- 7%, respectively; both P < 0.05) over the placebo time of 49.4 +/- 4.2 min, whereas there was no significant effect with 9 mg x kg–1 of caffeine. This was a surprising finding as the highest dose had the greatest effect on epinephrine, but could perhaps be explained that at this high dose some runners started to receive side effects.

Graham et al “Metabolic and exercise endurance effects of coffee and caffeine ingestion” J Appl Physiol 1998; 85: 883-9 (31% improvement with caffeine capsules, none with coffee)
Graham and colleagues studied the performance enhancing effects of ingesting 4.45 mg x kg–1 caffeine either in the form of coffee or as a caffeine capsule before running on a treadmill at 85% of VO2max in a double-blind cross-over trial of nine trained runners. Surprisingly, they found that despite similar plasma paraxanthine (a metabolite of caffeine) concentrations the endurance was only improved only after caffeine ingestion by capsules (9.9 min or 31% over that for placebo capsules), while the ingestion of caffeinated coffee did not enhance endurance. The reasons for this appears unclear, but the authors speculate that other substances in coffee known as chlorogenic acids may have antagonised the physiological responses of caffeine. However, the study has been widely criticized as the variability of the endpoint time to exhaustion is very high with a day to day coefficient of variation of ~27% and this could explain the lack of efficacy after coffee ingestion (Jeukendrup et al “A new validated endurance performance test” Med Sci Sports Exerc 1996; 28: 266–270). Using a more reproducible measurement with a cycling time trial performance, Hodgson and colleagues indeed showed similar performance enhancing effects of ingestion of 5 mg x kg–1 by either coffee or capsules and they found no evidence for an effect of chlorogenic acids in coffee (Hodgson et al “The Metabolic and Performance Effects of Caffeine Compared to Coffee during Endurance Exercise” PLoS ONE 2013; 8: e59561).

Candow et al “Effect of sugar-free Red Bull energy drink on high-intensity run time to-exhaustion in young adults” J Strength Cond Res 2009; 23: 1271–1275 (No effect)
Candow and colleagues studied in a placebo-controlled double-blind cross-over study the effects of ingesting sugar free Red Bull containing 2 mg x kg–1  caffeine in 17 physcially active college students performing a run-to-exhaustion trial at 80% VO2max. They could see no effects of the caffeine containing energy drink on run time, rate of perceived exhaustion or blood lactate levels .   

Ping et al “Effects of acute supplementation of caffeine on cardiorespiratory responses during endurance running in a hot & humid climate” Indian J Med Res 2010; 132; 36-41 (24% improvement)
An obvious drawback with the studies above is that the exercise time was very limited (less than 30 minutes) and therefore hardly applicable to endurance running. Another double-blind cross-over study was performed in hot and humid conditions (31°C, 70% relative humidity) at a lower VO2max of 70% in nine Malaysian trained runners after ingestion of either 5 mg x kg–1  or placebo. The mean run time to exhaustion was  prolonged after caffeine ingestion (110.1 ± 29.6 min versus and  83.6 ± 21.4 min after placebo ingestion) (P < 0.05), while heart rate, core body temperature, oxygen uptake and RPE did not differ between the groups. This was still a treadmill study, however, and I am not sure it can be applied to mountain ultramarathon trail running.

Walsh et al “Improved time to exhaustion following ingestion of the energy drink Amino Impact” J Int Soc Sports Nutr 2010; 7: 14 (12.5% improvement)
A double-blind cross-over study of 15 recreationally active college students running at 70% VO2max on a treatmill until exhaustion after ingestion of intake of either placebo or the energy drink “Amino Impact™” containing among other ingredients 2.05 g of caffeine, taurine and glucoronalactone. The run time to exhaustion was improved by 12.5% in the Amino Impact group compared to placebo.

Rahnama et al “The effectiveness of two energy drinks on selected indices of maximal cardiorespiratory fitness and blood lactate levels in male athletes” J Res Med Sci 2010; 15: 127-132 (10% improvement)
In this blinded cross-over study study ten male student athletes performed three maximal Bruce running tests with increasing speed and gradient until exhaustion on a treadmill 40 minutes after ingestion of placebo or the energy drinks Red Bull and Hype to a caffeine concentration of 6 mg x kg–1. Both energy drinks showed improvement in time to exhaustion of 10.5% (Red Bull) and 9.7% (Hype) compared to placebo.

Peltier et al “Effects of carbohydrates-BCAA-caffeine ingestion on performance and neuromuscular function during a 2-h treadmill run: a randomized, double-blind, cross-over placebo-controlled study” J Int Soc Sport Nut 2011; 8: 22 (1.8% improvement)
In this study thirteen moderately trained athletes were running for 2 hours at a treadmill after ingestion of either placebo or a sport drink containing carbohydrates, branched chain amino acids and caffeine (75 mg x L-1). There was a significant improvement of 1.8% in running distance after ingestion of the sport drink (22.31 ± 1.85 km) compared to placebo (21.90 ± 1.69 km). It is of course unclear from this study whether the effects are due to the carbohydrate/energy ingestion, the BCAA content or the caffeine in the sports drink.


5-10 km running trials

Bell et al “Effect of ingesting caffeine and ephedrine on 10-km run performance” Med Sci Sports Exerc. 2002; 34: 344-9 (No effect)
In this double-blind cross-over study, 12 recreational runners performed a 10-km trial on a treadmill while wearing wearing a helmet and a backpack weighing 11 kg after ingestion of placebo, caffeine 4 mg x kg–1, efedrine 0.8 mg x kg–1 or caffeine 4 mg x kg–1 and efedrine 0.8 mg x kg–1.  This study showed an effect on ephedrine on the run time, but an ergogenic effect of caffeine was not evident either when the drug was administered alone or in combination with ephedrine.

Umaña-Alvaradoa & Moncada-Jiméneza “Consumption of an ‘Energy Drink’ does not Improve
Aerobic Performance in Male Athletes” Int J Appl Sport Sci 2005; 17: 26-34 (No effect)
A double-blind cross-over study in 11 male athletes running a 10-km cross-country trial after ingestion of placebo or an energy drink containing 1.9 mg x kg–1caffeine. No effects could be seen of the drink on race times between the energy drink (45:40.95 ± 04:16.86 min) or placebo (46:07.33 ± 04:16.47 min).

Bridge & Jones “The effect of caffeine ingestion on 8 km run performance in a field setting” J Sports Sci. 2006; 24: 433-9 (1.2% improvement)
A double-blind cross-over study by Bridge and Jones of 8 trained male runners performing a 8-km time trial in an “ecologically valid” field setting after ingesting either a placebo capsule, a caffeine capsule with 3 mg x kg–1  caffeine or no supplement. Caffeine resulted in a mean improvement of 23.8 s (95% confidence interval [CI] = 13.1 to 34.5 s) in 8 km performance time (1.2% improvement, 95% CI = 0.7 to 1.8%).

O’Rourke et al “Caffeine has a small effect on 5-km running performance of well-trained and recreational runners” J Sci Med Sport 2008; 11: 231-233 (1.0% improvement)
In a double-blind cross-over study by O’Rourke and colleagues of 15 well-trained runners and 15 recrational runners performing a 5-km time trial on a 400m athletics track after either ingesting 5 mg x kg–1  caffeine or placebo tablets a significant effect on running performance was observed in both groups after caffeine intake. The improvements were moderate, however, with time to complete the 5-km improved by 1.0% (CI 0.4 – 1.6%) (1058 ± 68s vs 1047 ±69 s, i.e. 11 seconds improvement) for the well-trained runners and with 1.1% (CI 0.2 – 2%) for the recreational runners.

Schubert et al The effects of caffeinated “Energy Shots” on time trial performance Nutrients 2013; 5: 2062-2075 (No effect)
A blinded cross-over study where six elite trained runners were running 5-km as fast as possible on a treadmill after ingesting either a Red Bull Energy Shot (80 mg caffeine), a Yerba Maté Organic Energy Shot (140 mg caffeine) or placebo showed no differences in running performance. Of note is that the dose of caffeine administered in this study (1.43–2.5 mg x kg–1  for the lightest participant and 0.95–1.66 mg x kg–1  for the heaviest participant) and also the run-to-exhaustion study by Candow with a Red Bull drink is lower than normally recommended ergogenic doses of >2.5 mg x kg–1  (Ganio  et al “Effect of caffeine on sport-specific endurance performance: a systematic review” J Strength Condition Res 2009; 23: 315-24).


15-21 km and >1.5 hour running trials

Cohen et al “Effects of caffeine ingestion on endurance racing in heat and humidity” Eur J Appl Physiol Occup Physiol. 1996; 73: 358-63 (No effect)
In a double-blind cross-over study Cohen and colleagues studied the effects of  0, 5, or 9 mg x kg–1 body mass caffeine pre-race in 5 trained male and 2 female runners during  three maximal effort 21 km half-marathon runs in hot and humid conditions. They did not see any effects on rate of perceived exertion (RPE) or performance at either dose compared with placebo.

van Nieuwenhoven “The effect of two sports drinks and water on GI complaints and performance during an 18-km run” Int J Sports Med 2005; 26: 281-5 (No effect)
A similar lack of performance enhancing effect of caffeine was seen in another double-blind cross-over study of 98 trained runners by Van Nieuwenhoven and colleagues. The runners performed a competitive 18-km run three times within 8 days while taking either pure water, plain 7% carbohydrate (CHO) sport drink or a 7% CHO sport drink with ~1.3 mg x kg–1 coffeine in 7% CHO sport pre-exercise and at 4.5, 9, and 13.5 km during each race.

Tauler et al “Effects of caffeine on the inflammatory response induced by a 15-km run competition” Med Sci Sports Exerc 2013; 45: 1269-1276 (No effect)
A double-blind parallel group study in 33 runners completing a 15-km run competition taking either placebo (n = 16) or caffeine 6 mg x kg–1 (n = 17). The study was not designed and randomized to compare the two groups with regards to performance enhancing improvement and no differences were found. Caffeine supplementation induced higher levels of IL-6 and IL-10 in response to the run and the authors speculate that this might enhance an anti-inflammatory response.

 
In summary, there are certainly no impressive findings of caffeine as a performance enhancing aid in long-distance running and most studies, in particular on longer distances come out negative. On the other hand, the ability of acute caffeine to address cognitive related sleep deficits is reasonably well established also in an exercise setting (McLellan et al “Caffeine improves physical performance during 24 h of active wakefulness” Aviat Space Environ Med 2004; 75: 666-72). There are also no major side effects of caffeine intake, in particular if you are used to drink coffee regularly. However, a good recommendation is to try it before the most important race. On the other hand even if caffeine-naive individuals often have more adverse effects, they might also experience  a greater ergogenic effect (Bell & McLellan “Exercise and endurance 1, 3, and 6 hours after caffeine ingestion in users and nonusers” J Appl Physiol 2002; 93: 1227-1234).

Of course the caffeine can come from many sources and more tolerable for at least my stomach than coffee appear to be Coca-Cola during races. It contains about 45 mg caffeine per 12 oz (375 mL) can, and appear also to enhance endurance cycling performance during the later stages of a 2 hour time trial. The authors of that study speculate that this is due to the resulting caffeine intake of 1.5 mg x kg–1 (Cox et al “Effect of different protocols of caffeine intake on metabolism and endurance performance” J Appl Physiol  2002; 93: 990–999). There is of course caffeine in a lot of other products, including many energy gels, see figure below.



The caffeine content of various drinks (From Burke 2008). The sources were Centre

for Science in the Public Interest webpage http://www.cspinet.org/new/cafchart.htm and USDA National Nutrient Database webpage http://www.nal.usda.gov/fnic/foodcomp/search/ ) See also list at http://fellrnr.com/wiki/Caffeine.
 
One issue might be that most mountain ultramarathon races occurs at high altitudes and I have encountered the belief that coffee should be avoided when ascending to these altitudes. No studies prove this, however, and, iInterestingly, it has on the contrary in one study been speculated that caffeine might have particularly beneficial effects on high altitude due to its effect on ventilation and cerebral circulation and its action as a psychostimulant. (Hackett “Caffeine at high altitude: java at base camp” High Alt Med Biol. 2010; 11: 13-7). In travelers to high altitude, abrupt cessation of caffeine intake might lead to withdrawal symptoms  very similar to acute mountain sickness (AMS) and can be misdiagnosed as AMS. I guess the same thing might be seen in for habitual coffee drinking ultramarathon runners abruptly avoiding coffee during longer races.

Lastly, is coffee and caffeine dehydrating? Despite warnings that caffeine has negative effects on hydration status, electrolyte balance, and thermoregulation, Armstrong  and colleagues in a review of 75 years of literature, found that the evidence does not support these concerns (Armstrong et al “Caffeine, fluid-electrolyte balance, temperature regulation, and exercise heat tolerance” Exerc Sport Sci Rev 2007; 35: 135-140). A recent study by Killer and colleagues come to the same conclusions as they show by measuring a wide range of haematological and urinary markers of hydration in a cross-over study of 50 male habitual coffee drinkers (consuming 3-6 cups per day) that coffee provides similar hydrating qualities as water (Killer et al “No evidence of dehydration with moderate daily coffee intake: A counterbalanced cross-over Study in a free-living population. PLoS ONE 2014; 9: e84154). So, no it appears again that if you are used to drinking coffee normally it should be fine to drink also during an ultramaraton race. Despite lack of current scientific evidence for the benefits I will continue to do that. And I hope I at least once again in my life will experience another cup as the one I had on Col Brison.

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