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2 REVIEW The impact of caffeine on mood, cognitive function, performance and hydration: a review of benefits and risks C. H. S. Ruxton Nutrition Communications, Cupar, UK Summary The reputed benefits of moderate caffeine consumption include improvements in physical endurance, cognitive function, particularly alertness and vigilance, mood and perception of fatigue. In contrast, there are concerns that excessive intakes increase the risks of dehydration, anxiety, headache and sleep disturbances. This paper is a review of double-blind, placebo-controlled trials published over the past 15 years to establish what range of caffeine consumption would maximise benefits and minimise risks for cognitive function, mood, physical performance and hydration. Of the 41 human studies meeting the inclusion criteria, the majority reported benefits associated with low to moderate caffeine intakes (37.5 to 450 mg per day). The available studies on hydration found that caffeine intakes up to 400 mg per day did not produce dehydration, even in subjects undergoing exercise testing. It was concluded that the range of caffeine intake that appeared to maximise benefit and minimise risk is 38 to 400 mg per day, equating to 1 to 8 cups of tea per day, or 0.3 to 4 cups of brewed coffee per day. The limitations of the current evidence base are discussed. Keywords: caffeine, cognitive function, mood, performance, risk Introduction Caffeine (1,3,7-trimethylxanthine) is the most consumed psychoactive substance in the world. Although caffeine is naturally present in many plant-based foods, the main sources in the Western diet are coffee, tea, cocoa products and cola products. Table 1 provides typical caffeine levels found in standard portions of these. The wide variation in the caffeine content of tea and coffee can be explained by differences in the blend Correspondence: Dr Carrie H. S. Ruxton, Freelance Dietitian, 6 Front Lebanon, Cupar KY15 4EA, UK. carrie@nutrition-communications.com and brewing times (FSA 2004). Caffeine is used as a stimulant in traditional South American and African communities via consumption of caffeine-rich plant products, such as cola nut and maté. It is also used in supplements and drinks designed for weight management, sports performance or energy boosting, and in some medicines (e.g. cold and flu remedies). Most of the average UK caffeine intake of 4 mg per kg bodyweight originates from tea (Thomas 2003). Caffeine is rapidly absorbed from the gastrointestinal tract, with plasma levels peaking at minutes postingestion. Urine is a poor method of assessing caffeine exposure, as less than 6% of a caffeine dose is excreted (Thomas 2003). Instead, caffeine is metabolised, mostly 15

3 16 C.H.S. Ruxton Table 1 Caffeine content (mg/serving) of commonly consumed beverages Beverage (serving size) Range Average Tea (190 ml) Instant coffee (190 ml) Ground coffee (190 ml) Hot chocolate (150 ml) 1 6 Dark chocolate (bar) 50* Cola (330 ml) Energy drink (250 ml) Source: compiled from FSA (2004) and product information. Average values from FSA website. *Milk chocolate contains about half as much caffeine. in the liver by the P45 enzyme system, producing a range of metabolites, including dimethylxanthine, monomethylxanthine and uric acid. The average half-life of caffeine is 2.5 to 4.5 hours but can vary from 1 to 10 hours in certain individuals (ANZFA 2000). The Food Standards Agency (FSA 2001) advises pregnant women to limit their caffeine intake to a maximum of 300 mg per day owing to concerns that excessive caffeine may cause miscarriage or low birthweight. There are no official recommendations to limit caffeine consumption in non-pregnant consumers, although this has not prevented the assumption by media commentators and others that caffeine can be harmful. Specifically, it is claimed that regular caffeine consumption, even at moderate levels, increases the risk of dehydration, anxiety and sleep disorders. While the published literature contains examples of high-dose caffeine studies where negative effects have been found (e.g. Smith 2002), there is also a considerable body of literature suggesting that natural caffeine-containing foods and beverages offer cognitive and performance-related benefits, and may provide a source of polyphenols (Gardner et al. 2007). This review aims to examine and collate double-blind, placebo-controlled trials in order to investigate the risks and benefits of regular caffeine consumption on mood, cognitive function, physical performance and hydration. Methods Medline was searched for English-language, peerreviewed studies published between 1992 and Search terms included caffeine in combination with mood, cognitive function, hydration, diuresis, performance and exercise. Inclusion criteria were that studies had to be on healthy adults and that a doubleblind, placebo-controlled methodology was used. The focus on placebo-controlled experiments was important as regular caffeine consumers may be conditioned to anticipate cognitive effects from caffeinated products (Smit et al. 2006). Studies using combinations of caffeine and other substances (e.g. glucose, herbs and drugs) were excluded unless the results for caffeine vs. placebo could be extracted. The use of caffeinecontaining beverages as test products was allowed if similar non-caffeinated products were used as controls. However, it is acknowledged that decaffeinated tea and coffee are not actually caffeine-free and can contain up to 8 mg caffeine per cup (FSA 2004). Meta-analyses were included but were used only to support the discussion. Reference lists of acceptable papers were hand searched in an attempt to locate all relevant studies. Mood and cognitive performance Caffeine is believed to impact on mood and performance by inhibiting the binding of both adenosine and benzodiazepine receptor ligands to brain membranes. As these neurotransmitters are known to slow down brain activity, a blockade of their receptors lessens this effect. Caffeine intake also causes changes to a variety of other neurotransmitters, including noradrenaline, dopamine, serotonin, acetylcholine, glutamate and gamma-aminobutyric acid (Fredholm et al. 1999). Twenty-three studies were found and are summarised in Table 2. These considered a range of cognitive measures, such as memory, accuracy, vigilance and speed, as well as self-reported mood and perceived fatigue. A typical study would involve volunteers being given a placebo, or one or more doses of caffeine in drinks/ capsules. Mood and cognitive tests (often using computer software) would be undertaken at baseline and shortly after consumption of the placebo/caffeine. Before and after test results could then be compared to look for differences that may relate to caffeine consumption. Sixteen of the studies in Table 2 were on healthy, rested subjects and, of these, 14 reported benefits relating to caffeine consumption, including improved alertness, short-term recall and reaction time. There were also consistent findings for positive mood and lower perceived fatigue. The caffeine dose varied depending upon the study, with most using a single bolus of caffeine, ranging from 37.5 to 450 mg. A few studies considered caffeine intake over several days using doses of 1 to 6 mg per kg bodyweight, taken up to four times daily. The maximum caffeine dose for the longer studies, assuming a typical 70 kg person, was in the region of 450 mg. While the duration of most of the studies may

4 Caffeine: a review of benefits and risks 17 Table 2 Caffeine and mood/cognitive function Reference Subjects Caffeine test Outcome variables Results for caffeine vs. placebo* Not sleep-restricted Haskell et al. (2005) 24 habitual caffeine users following 24-hour abstinence vs. 24 non-users Heatherley et al. (2005) 49 habitual caffeine users following 4-, 6- or 8-hour abstinence Smit & Rogers (2000) 23 habitual caffeine users following 24-hour abstinence. Within-person study Robelin & Rogers (1998) 64 habitual caffeine users following 24-hour abstinence Yeomans et al. (2002) 30 habitual caffeine users preloaded with 0,1 or 2 mg/kg bodyweight caffeine Childs & de Wit (2006) 102 light caffeine users. Within-person study Smith et al. (2005) 60 habitual caffeine users. Normal consumption maintained before trial Christopher et al. (2005) 68 habitual caffeine users. Normal consumption maintained before trial Brice & Smith (2002) 24 habitual caffeine users. Within-person study involving decaffeinated coffee + added caffeine 75-, 150-mg bolus Cognitive performance, mood Improvements in reaction time, vigilance, memory. Habitual users outperformed non-users 1.2 mg/kg BW bolus Cognitive performance, psychomotor skills, mood Caffeine had short-term stimulant effects after 8-hour abstinence. Not all were positive 12.5-, 25-, 50-, 100-mg bolus Cognitive performance, thirst, mood Caffeine improved cognitive function 1.2 mg/kg BW given t.i.d. in novel fruit drink Hindmarch et al. (2000) 30 habitual caffeine users 37.5, 75, 100 mg q.i.d. to mimic tea/ coffee intake Hindmarch et al. (1998) 19 habitual caffeine users. Within-person study Quinlan et al. (2000) 32 habitual caffeine users. Within-person study Smith et al. (2006) 25 habitual caffeine users following 24-hour abstinence vs. 25 non-users Psychomotor skills and mood tested after drink to assess cumulative effect 0 vs. 1 mg/kg BW bolus Cognitive performance, alertness, mood 50-, 150-, 450-mg bolus Memory, reaction time, vigilance, mood at all doses. Regular caffeine users benefited more than low users Caffeine improved cognitive function after one exposure. No cumulative effect Performance improved after 1st dose of caffeine but not after 2nd Performance enhanced and mood improved in short-term 1.5 mg/kg BW bolus Cognitive performance, mood Performance and mood improvements. Dose response. Intra-individual differences 2 mg/kg BW bolus Cognitive performance, mood Performance and mood improvements 65 mg q.i.d. vs. 200-mg bolus Cognitive performance, mood Both regimes improved performance and increased reported anxiety Cognitive performance, sleep quality Both regimes improved performance but higher doses of caffeine disrupted sleep 100-mg bolus as tea, coffee or Cognitive performance Alertness maintained with caffeine. caffeinated water Tea and coffee had similar effects 25-, 50-, 75-, 100-, 200-mg bolus Blood pressure, mood, alertness Caffeine increased blood pressure and elevated mood. No dose response 2 mg/kg BW bolus Cognitive performance, mood Performance and mood improvements regardless of caffeine withdrawal

5 18 C.H.S. Ruxton Table 2 Continued Reference Subjects Caffeine test Outcome variables Results for caffeine vs. placebo* Hewlett & Smith (2006) 120 habitual caffeine users following 24-hour abstinence vs. 56 infrequent users Judelson et al. (2005) 60 subjects after 3 day of caffeine equilibration (3 mg/kg bodyweight/ day) James (1998) 36 habitual caffeine users 1- vs. 6-day exposure mg/kg BW t.i.d. 1 mg/kg BW bolus Cognitive performance Performance and mood improvements regardless of caffeine withdrawal. Caffeine users benefited more than infrequent users 3 or 6 mg/kg BW/day for 5 days Cognitive performance, psychomotor skills, mood Sleep-restricted Lieberman et al. (2002) 68 sleep-deprived US Navy trainees 100-, 200-, 300-mg bolus Vigilance, reaction time, marksmanship, alertness No effects Cognitive performance, alertness Acute improvements in alertness, not sustained over 6 days. No effect on cognitive performance Deslandes et al. (2006) 10 sleep-restricted subjects 400-mg bolus Cognitive performance No effects Rogers et al. (2005) 17 habitual caffeine users following 3-week abstinence vs. 17 habitual caffeine users following 24-hour abstinence. Both groups sleep-restricted James et al. (2005) 96 habitual caffeine users alternating between 4-week caffeine use and 4-week placebo. Rested vs. sleep-restricted James & Gregg (2004) 48 habitual caffeine users alternating between 4-week caffeine use and 4-week placebo. Rested vs. sleep-restricted 1.2 mg/kg BW bolus Cognitive performance, psychomotor skills 1.75 mg/kg BW bolus Cognitive performance, psychomotor skills, mood Improvements in all except marksmanship. Effects greatest one hour post consumption No effects over and above withdrawal alleviation No effects over and above withdrawal alleviation 1.75 mg/kg BW t.i.d. Mood Some subjects experienced poorer mood scores after caffeine van Duinen et al. (2005) 23 fatigued subjects 3 mg/kg BW bolus Cognitive performance Caffeine partly prevented fatigue-related cognitive decline Tikuisis et al. (2004) 20 military personnel. Control vs. sleep-deprived 600 mg Cognitive performance around shooting skills All measures of performance declined with sleep deprivation. Caffeine restored some measures but not marksmanship *Only statistically significant findings reported. BW, bodyweight; q.i.d., four times a day; t.i.d., three times a day.

6 Caffeine: a review of benefits and risks 19 appear short, it is worth bearing in mind that plasma caffeine levels peak at minutes post-ingestion. Thus, any cognitive effects would be expected to occur in the short-term. The issues of tolerance and dose response are addressed later in this review. Sleep deprivation is known to affect cognitive function and mood. Seven studies examined the impact of caffeine on sleep-restricted subjects, with only three finding that caffeine restored at least some measures of cognitive function. A single study by James and Gregg (2004) reported a negative impact of caffeine in sleeprestricted subjects. The dose of caffeine used in these studies ranged from 84 to 600 mg per day, usually taken as a single bolus. It has been argued that regular exposure to caffeine could increase tolerance to cognitive and mood effects (Childs & de Wit 2006). This point was addressed by a number of studies involving comparisons between habitual users of caffeine and low/non-users. In most of these, habitual users appeared to experience greater cognitive or mood effects compared with low/non-users, which is surprising as tolerance would be expected to blunt any effects. This was even the case when the caffeine was supplied as capsules, rather than tea or coffee, which could have raised expectations among regular consumers of these beverages. Smit and Rogers (2000) found that habitual caffeine users demonstrated tolerance to the thirst-inducing effects of caffeine but not to the performance-enhancing and mood effects. There is controversy about whether or not the cognitive effects associated with caffeine consumption are related to withdrawal alleviation. Supporters of this theory (e.g. Yeomans et al. 2002; James & Gregg 2004) suggest that caffeine withdrawal in habitual users worsens cognitive function while re-introduction of caffeine simply restores cognitive function to baseline levels, thus offering no additional benefit (see Rogers 2007). Those in opposition to this theory (e.g. Smith et al. 2005; Childs & de Wit 2006) cite experimental examples where subjects, regardless of exposure to withdrawal, experience cognitive and mood enhancements with caffeine consumption. Among the studies collated for this review, opinion was evenly split, although it is worth noting that most of the studies supporting the withdrawal alleviation theory were carried out on sleep-deprived subjects, which may have influenced the results. If it is assumed that caffeine does have a real impact on cognitive function, it is logical to consider whether a dose response exists. Of the 15 studies that compared different levels of caffeine intake, only two reported a dose response for cognitive performance (Lieberman et al. 2002; Smith et al. 2005), while a further two found a dose response for blood pressure, heart rate or skin temperature (Hindmarch et al. 1998; 2000). In the latter study, coffee (moderate/high caffeine) adversely affected sleep onset and duration, while tea (low/ moderate caffeine) did not. It was clear that the majority of studies did not support a dose response argument and that the first exposure to caffeine appeared to induce the cognitive and mood effects. Heatherley et al. (2005) simulated normal consumption of caffeinated beverages, finding that the second cup did not induce further cognitive or mood benefits until at least 8 hours had elapsed. The level of caffeine intake at which cognitive effects were generated was fairly low in terms of normal daily consumption patterns. In the study by Smit and Rogers (2000), the lowest dose was 12.5 mg, which equates to one third of a cup of tea. This finding is backed up by other reviews (ANZFA 2000). In studies of caffeinated beverages, tea and coffee produced similar cognitive and mood effects, but differed in terms of other outcomes (e.g. sleep quality, heart rate, blood pressure). This could suggest that cognitive function is not influenced by increasing caffeine dose, while other physiological systems are. It may also reflect differences in the presence of other biologically active components in tea and coffee (e.g. flavonoids, theophylline or theobromine). Indeed, some authors have noted that the cognitive/mood effects of tea and coffee are not fully explained by the caffeine content (Hindmarch et al. 1998; Quinlan et al. 2000). Physical performance Until 2004, the International Olympic Committee (IOC) restricted caffeine use during competition as it was believed to be an ergogenic (i.e. performance-enhancing) compound. The maximum permitted level was 12 mg caffeine per litre of urine (equivalent to around 5 cups of coffee). A review of the World Anti-doping Code in 2003 reversed the ban (World Anti-doping Agency 2003), although caffeine is still considered to be ergogenic even at levels below the former IOC threshold (Graham 2001; Schwenk & Costley 2002). Caffeine is thought to impact on physical and sporting performance via one or more modes of action. A commonly cited mechanism links caffeine consumption to increased free fatty acid oxidation, which would have the effect of sparing glycogen and prolonging the duration of exercise (Nehlig & Debry 1994; Paluska 2003). Certainly, caffeine ingestion has been found to increase plasma free fatty acids and promote insulin resistance (Norager et al. 2005). However, this proposed mecha-

7 20 C.H.S. Ruxton nism is disputed by some researchers (Graham 2001). Other mechanisms include enhancing muscle contractions via changes to sodium, calcium and potassium concentrations (Magkos & Kavouras 2005), and increased tolerance to fatigue via production of plasma catecholamines and inhibition of adenosine receptors (Nehlig & Debry 1994). Eleven studies were found that met our criteria, and these are summarised in Table 3. Five used trained subjects, while one was on active elderly people. The majority of studies found that caffeine consumption, at intakes of 2.5 to 6 mg per kg bodyweight, enhanced physical performance. Outcome measures included time to exhaustion, running/cycling performance, perception of fatigue and cycling power. In the two studies where a null effect was found, one gave 34 students 201 mg per day of caffeine for 8 weeks (Malek et al. 2006), while the other gave 8 trained cyclists 6 mg per kg bodyweight per day (Hunter et al. 2002). The latter authors wondered whether the lack of effect was due to the cyclists performing over a fixed distance, rather than cycling to exhaustion, as this type of protocol would not have picked up any impact of caffeine consumption on endurance. It would appear, from the available evidence, that caffeine has ergogenic properties and, indeed, this is the view taken by two meta-analyses by the same authors. Doherty and Smith (2004) examined the evidence from 40 double-blind studies on exercise performance, finding that caffeine improved exercise test performance by 12%. The effect was more pronounced for endurance exercise than for graded or short-term exercise. The second meta-analysis (Doherty & Smith 2005) examined the impact of caffeine ingestion on perceived exertion using data from 21 studies. It was reported that the lower ratings of perceived exhaustion relating to caffeine ingestion accounted for 30% of the improvement in exercise performance. The authors proposed that the impact of caffeine on ratings of perceived exhaustion could partly explain its ergogenic effects. Habitual intake of caffeine does not appear to diminish any ergogenic properties (Paluska 2003). Hydration It is a common perception that caffeine-containing drinks cause a net loss in fluid and may lead to dehydration. FSA advice (2007) states: Drinks that contain caffeine (such as tea, coffee and cola) can act as diuretics, which means they can make your body lose greater volumes of water than usual. So these drinks can lead to an increased need for water or other fluids that don t have a diuretic effect. If this were the case, large numbers of UK adults would be at risk from dehydration because 70 97% are regular consumers of caffeinated beverages (Henderson et al. 2002; Heatherley et al. 2006). According to the National Drinks Survey (Taylor Nelson Sofres 2007), average intakes of tea and coffee in UK adults are 2.1 and 1.1 cups per day, respectively. Any risk of dehydration would be higher in elderly people, who, on average, consume 85% of daily nonfood fluid from tea (Taylor Nelson Sofres 2003). In theory, caffeine could have an adverse effect on hydration as it increases blood flow to the kidneys and inhibits the re-absorption of sodium, calcium and magnesium, thus expelling more water (Birkner et al. 2006). There is also epidemiological evidence that caffeine consumption provokes the need to urinate by stimulating the bladder s detrusor muscles (Arya et al. 2000), although this was not confirmed by a randomised controlled trial in women with detrusor overactivity (Swithinbank et al. 2005). However, the theory may not translate into practice because much of the research used high caffeine intakes in the form of capsules, rather than caffeinated beverages, and mechanistic studies were performed in rats. Despite the view that caffeine may act as a diuretic, there were surprisingly few studies in humans. Table 4 gives details on the eight studies found. In five of these, a daily caffeine intake of 1.4 to 6 mg per kg bodyweight (98 to 420 mg per day for an average 70 kg person) did not have an adverse effect on hydration. Caffeine intakes were substantially higher in two studies that did find evidence of dehydration. Wemple et al. (1997) used a dose of 8.75 mg per kg bodyweight, finding that urine output increased by 400 ml compared with the placebo condition when subjects (n = 8) were at rest. Interestingly, no significant differences in hydration were seen when subjects performed a three hour cycle test, and the authors proposed that this may have been due to elevated catecholamine levels. Neuhauser-Berthold et al. (1997) compared six cups of coffee (providing 642 mg caffeine) with a water placebo in 12 non-exercising subjects who had been deprived of caffeine for five days. Over the four hour trial, urine output increased in the caffeine group by 753 ml, and there was evidence of dehydration from bodyweight and body water estimates. Excretion of both sodium and potassium increased. A further study (Bird et al. 2005) reported increased urine output (360 ml) on day one, but not on days 2 or 3, of a trial of 5.6 mg caffeine per kg bodyweight. This suggests tolerance to the renal effects of caffeine after 48 hours. These studies taken together suggest that higher levels of caffeine can cause dehydration, particularly when subjects have abstained from the

8 Caffeine: a review of benefits and risks 21 Table 3 Caffeine and physical performance Reference Subjects Caffeine test Outcome variables Results for caffeine vs. placebo* Malek et al. (2006) 34 students undergoing 8-week aerobic training 201 mg/day for 8 weeks VO2 peak, running time to exhaustion No effect Wiles et al. (2006) 8 trained cyclists 5 mg/kg BW bolus Cycling speed and power Speed and power improved Beck et al. (2006) 37 resistance-trained men 201 mg bolus Muscular endurance, anaerobic capability Weight lifted in the one repetition bench press increased by 2 kg Norager et al. (2005) 30 healthy elderly subjects. Within-person study. 48-hour abstention from caffeine 6 mg/kg BW bolus Cycling and upper body endurance, walking speed Endurance improved Bridge & Jones (2006) 8 male distance runners. Cross-over design 3 mg/kg BW bolus 8-km run performance, blood lactate Performance greater. Blood lactate levels higher 3 minutes after exercise Stuart et al. (2005) 9 male rugby players. Cross-over design 6 mg/kg BW bolus Simulation of rugby performance Speed, power and passing accuracy improved. Perceived fatigue lower McLellan et al. (2004) 16 subjects after 28 hours of sleep 600 mg taken over 7.5 hours Marching endurance, running time to Perceived exertion lower during march. deprivation in military-style setting exhaustion Time to exhaustion increased Bell & McLellan (2003) 9 male caffeine users 2.5, 5 mg/kg BW bolus Cycling endurance Time to exhaustion increased after both doses of caffeine Hunter et al. (2002) 8 trained cyclists 6 mg/kg BW preload followed by 100-km cycling time trial No effect 0.33 mg/kg BW every 15 minutes during trial Bell & McLellan (2002) 13 habitual caffeine users vs. 8 non-users 5 mg/kg BW bolus taken 1, 3 or 6 hours prior to exercise Wemple et al. (1997) 6 trained cyclists. Cross-over design in resting condition and after 3-hour cycling Cycling endurance Time to exhaustion increased when caffeine taken 1 or 3 hours prior to exercise. Effects greater in non-users 8.75 mg/kg BW taken over 4-hour period Maximal performance at 85% VO2 max No impact *Only statistically significant findings reported. BW, bodyweight.

9 22 C.H.S. Ruxton Table 4 Caffeine and hydration Reference Subjects Caffeine test Outcome variables Results for caffeine vs. placebo* Wemple et al. (1997) 6 trained cyclists. Cross-over design in resting condition and following 3-hour cycling 8.75 mg/kg BW taken over 4-hour period Fiala et al. (2004) 10 partially heat-acclimated athletes Caffeinated (mean 244 mg/day) vs. caffeine-free cola Armstrong et al. (2005) 59 healthy men following 6-day equilibrium on 3 mg/kg BW Bird et al. (2005) 80 habitual caffeine users following 24-hour abstinence Falk et al. (1990) 7 trained male athletes. Cross-over design Roti et al. (2006) 59 active male students following 6-day equilibrium on 3 mg/kg BW Grandjean et al. (2000) 18 healthy adult men. Cross-over design of 4 commercially-available test drinks Neuhauser-Berthold et al. (1997) 12 healthy volunteers after 5-day abstention from methylxanthines Fluid-electrolyte balance Urine output 400 ml greater at rest. No differences during exercise Hydration following 2 x 2 hour exercise sessions 5-day test period of 3 or 6 mg/kg BW Fluid-electrolyte balance, urine colour, body mass No impact on hydration apart from urine colour (darker after caffeine) No impact on hydration 3-day regime of 5.6 mg/kg BW/day Fluid balance Urine output 360 ml greater on day 1. No differences on days 2 and 3 5 mg/kg BW preload followed by 2.5 mg/kg BW 2 and 0.5 hours prior to exercise 5-day test period of 3 or 6 mg/kg BW with exercise test 1-day test periods of mg/day ( mg/kg BW) 1-day test of 6 cups of coffee (642 mg caffeine/day) Thermoregulation, fluid balance post exercise Fluid-electrolyte balance, thermoregulation post exercise No impact No impact Fluid-electrolyte balance, body mass No impact. BW reduced in all fluid conditions Fluid-electrolyte balance, BW, TBW (estimated by BIA) 24-hour urine output increased by 753 ml. BW reduced by 0.7 kg.tbw reduced by 2.7%. Na and K urinary excretion increased *Only statistically significant findings reported. BIA, bioelectrical impedance analysis; BW, bodyweight; TBW, total body water.

10 Caffeine: a review of benefits and risks 23 substance for a number of days. There is no evidence at present that low to moderate intakes of caffeine, even when consumed around extreme exercise, affect hydration in a negative way. Safe limits and applications In the studies reviewed here, different levels of caffeine had different effects. The maximum daily caffeine dose in the cognitive studies, assuming a typical 70 kg person, was in the region of 450 mg. Enhancements in mood and cognitive function were seen following daily caffeine intakes of 37.5 to 450 mg, although some disturbances to sleep were seen at around 400 mg per day. Turning to the physical performance data, intakes of 2.5 to 6 mg per kg bodyweight (equivalent to 175 to 420 mg per day for an average person) improved measures of endurance, power and tolerance of fatigue. Finally, the available studies on hydration found no ill effects of caffeine at intakes up to 400 mg per day, although it is acknowledged that these studies were relatively few in number. Thus, the range of caffeine intake that would appear to maximise benefit while minimising risk, in relation to the topics covered by this review, seems to be 38 to 400 mg per day. This would be in the low to medium range according to an Australian/New Zealand expert group (ANZFA 2000). This group identified intakes of caffeine greater than 500 mg per day (>7 mg per kg bodyweight) as high. It is not known how many UK consumers exceed 400 mg per day, as data are currently unavailable. However, average caffeine intakes according to an ongoing study of 5870 adult consumers are 241 mg per day, with 97% of people identified as caffeine consumers (Heatherley et al. 2006). Given the average caffeine content of beverages (Table 1), a beneficial range of caffeine consumption would equate to a tea intake of 1 to 8 cups per day, a brewed coffee intake of 0.3 to 4 cups per day or an energy drink intake of 5 cans. Average tea and coffee consumption in the UK is within this range, at 2.1 cups per day for tea, and 1.1 cups per day for coffee (Taylor Nelson Sofres 2007). Recommendations have been made by a few organisations to help groups of people gain benefits from caffeine consumption. In the USA, military personnel are advised that 100 to 600 mg of caffeine can maintain cognitive performance during periods of sleep deprivation (Institute of Medicine 2001). The UK Department for Transport (2007) recommends that drivers consume two cups of coffee or another high-caffeine drink to help combat tiredness. There are no recommendations, as yet, for sports people. Limitations of the review Many of the available studies had small sample sizes, although the body of evidence was considerable for mood and cognitive function. However, the use of differing cognitive and mood tests made some comparisons challenging. The issue of whether caffeine merely reverses withdrawal symptoms or confers a real cognitive benefit remains controversial and is hard to resolve, because most people are now exposed to some dietary caffeine (Heatherley et al. 2006). Thus, studies need to be of sufficient duration to judge the long-term effects of caffeine, yet include caffeine consumers who have experienced sufficient abstinence to get beyond any impact of withdrawal alleviation. As mood and cognitive function are subjective variables, within-person comparisons are most appropriate. Finally, there are difficulties in translating any caffeine ranges from experimental evidence to real life owing to differences in how tea and coffee, the main sources of caffeine in the UK diet, are prepared by individual consumers. Conclusions From a review of double-blind, placebo-controlled studies published over the past 15 years, it would appear that the range of caffeine intake that could maximise benefit and minimise risk in relation to mood, cognitive function, performance and hydration is 38 to 400 mg per day, equating to 1 to 8 cups of tea, or 0.3 to 4 cups of brewed coffee per day. Current levels of caffeine intake in the UK fall well within this range, suggesting that risk, for example from dehydration, is likely to be minimal. Acknowledgements This review was made possible by a grant from the Tea Council (UK), a condition of which was that Tea Council representatives and associates played no role in writing the review. References Armstrong LE, Pumerantz AC, Roti MW et al. (2005) Fluid, electrolyte, and renal indices of hydration during 11 days of controlled caffeine consumption. International Journal of Sports Nutrition and Exercise Metabolism 15: Arya LA, Myers DL & Jackson ND (2000) Dietary caffeine intake and the risk for detrusor instability: a case-control study. Obstetrics and Gynecology 96: ANZFA (Australian New Zealand Food Authority) (2000) Report of the Expert Working Group on the Safety Aspects of Dietary Caffeine. ANZFA: Canberra/Wellington.

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