Coffee and brain

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The Coffee and Health Information Bureau (Voorlichtingsbureau voor Koffie
en Gezondheid) sought assistance from scientists who are well known for their
knowledge and experience in this research area. We would like to take this op-
portunity to thank them for their excellent contribution and cooperation in the
preparation of this brochure.

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Coffee and brain

  1. 1. Coffee and the brain
  2. 2. ColophonPublishingCoffee and Health Information BureauDesign and printingStimio Communicatie & Presentatie, Tiel, The NetherlandsCopyright© April 2011, Coffee and Health Information Bureau, Rijswijk, The NetherlandsAvailabilityThe brochure ‘Coffee and the brain‘ can be downloaded free of charge fromwww.koffieengezondheid.nl. From here, you can also download the brochure‘Coffee, heart and blood vessels’ (2007) and ‘Coffee, stomach, intestinesand liver’ (2009) or you can register for the email newsletter. This free Dutchnewsletter keeps you updated on the most recent scientific information oncoffee and health and is published 4 times a year.Coffee and Health Information Bureau(Voorlichtingsbureau voor Koffie en Gezondheid)P.O. Box 161, 2280 AD RijswijkTel. : + 31 (0)70 - 3365163Fax : + 31 (0)70 - 3365167E-mail: info@koffieengezondheid.nlWebsite: www.koffieengezondheid.nl
  3. 3. ‘Coffee and the brain’- Contents PageIntroduction 5-61 Coffee, caffeine and headache Headache 7 Caffeine and headache 8-9 Caffeine withdrawal, fasting and weekend headache 9-13 Headache and fluid balance 13 References 142 Coffee, caffeine en cognition Cognitive function 15-16 Caffeine and the brain 16-17 Coffee and alertness 17-19 Coffee and attention, concentration and memory 20-21 Coffee and qualification caffeine effect 21-22 Coffee and mood 23-24 Coffee and sleep 24 References 26-273 Coffee and cognitive aging Cognitive aging, MCI and dementia 29 Coffee and acute effects on cognitive aging 29-30 Coffee and long term effects on cognitive aging 30-31 Coffee and Alzheimer’s disease 31-32 Coffee and Parkinson’s disease 32-33 References 34Study of coffee and health 35 Coffee and the brain | 3
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  5. 5. IntroductionCoffee is not only appreciated for its taste and aroma, but also for its effect onthe mental performance. It’s widely known that coffee can help to stay alert, buthow much coffee do you have to drink before you notice any effect and what isknown about the mechanism? What is the effect of coffee on headache, does italleviate the symptoms or not? Coffee adds to cognition, but could coffee coun-teract age-related cognitive decline? This brochure deals with common ques-tions about coffee in relation to the effect on the brain and provides a summaryof results of innumerable scientific studies.The Coffee and Health Information Bureau (Voorlichtingsbureau voor Koffieen Gezondheid) sought assistance from scientists who are well known for theirknowledge and experience in this research area. We would like to take this op-portunity to thank them for their excellent contribution and cooperation in thepreparation of this brochure.- Dr. Astrid Nehlig (research director, Faculté de Médécine, French National Institute for Health and Medical Research, INSERM, Strasbourg, France)- Dr. Monicque Lorist (associate professor, Faculteit der Gedrags- en Maatschappijwetenschappen, Rijksuniversiteit Groningen, The Netherlands)- Dr. Jan Snel (associate professor UHD psychofysiology, Universiteit van Amsterdam, The Netherlands) Coffee and the brain | 5
  6. 6. Research on the effects of coffee and/or caffeine on cognitive aging is highly relevant and very timely due to the aging of the population. Some topics do not have yet an unequivocal answer, because the amount of research is currently insufficient. The Information Bureau will continue to closely monitor scientific developments and inform you on new studies in our email newsletter and on our website www.koffieengezondheid.nl. If after reading of this brochure you still have questions or comments, we will be pleased to hear from you. You can also order Dutch copies of the brochure free of charge or download the Dutch or English version at www.koffieengezond- heid.nl. Coffee and Health Information Bureau (Voorlichtingsbureau voor Koffie en Gezondheid)6|
  7. 7. 1 Coffee, caffeine and headache1 What is headache?Headaches occur as a response to daily life situations like stress, fatigue, lackof sleep, hunger or weather changes. Despite the fact that headaches areextremely common, almost 90% of men and 95% of women have at least oneheadache a year, they are not fully understood. Neither the skull nor the brain issensitive to pain, however, both are surrounded by pain-sensitive membranes.Abnormalities in these membranes or nearby muscles, blood vessels, or nerves,either alone or in combination, are thought to be the source of most headachepain. Also changes in estrogen level can make headaches worse (Harvard HealthPublications, 2010)2 What are the common types of headache?The International Classification of Headache Disorders (ICHD) separates primaryheadache disorders from the secondary headache disorders. The former include,most importantly, migraine, tension type headache and cluster headache. Thelatter is attributed to causative disorders like a head or neck trauma, a vasculardisorder, a substance (e.g. medication overuse), substance withdrawal (e.g.caffeine) or a disorder of homeostasis (e.g. fasting) (IHS, 2004; Olesen, 2004).Tension type headache and migraine are the most common types of headache;however, mixed headaches do occur. Coffee and the brain | 7
  8. 8. 3 Can caffeine consumption relief headache symptoms? Caffeine may act as analgesic for headache and the use of caffeine as constitu- ent of analgesics dates back to 1875. Nowadays caffeine is an essential com- ponent of numerous widely consumed medications for the relief of headache symptoms (Shapiro, 2008; Nehlig, 2004). A meta-analysis of 30 clinical trials indicates that adding caffeine to an analgesic agent reduces the dosage needed of that analgesic agent by 40% to achieve equivalent analgesia (Laska, 1984). A further meta-analysis of randomized controlled trials of simple analgesics taken with or without caffeine indicates that addition of caffeine promotes a significant headache relief (Zhang, 2001). Studies on the efficacy and safety of over the counter (OTC) headache combination analgesics were reviewed in 2010 (Anneken, 2010). Treatment of migraine and tension-type headache, was shown more effective using a combination of acetylsalicyclic acid (ASA), acetaminophen and caffeine (100-150 mg) than monotherapy with either of these substances. Adding caffeine was associated with an increased analgesic effect, which is often unachievable via increased dosages of mono-analgesics because of their flat dose-effect relationships. Moreover, mixed analgesics co- formulated with caffeine provide the same efficacy using a lower analgesic dose, thus potentially reducing dose dependent adverse effects. 4 Can you get a headache of too much caffeine? Conflicting results have been found in population studies evaluating the association between high caffeine consumption and the prevalence of headache and chronic frequent headache (CFH), in particular. CFH is the collective term for primary headaches occurring on more than 14 days per month for at least 3 months. In a general population study in the Netherlands, CHF was associated with overuse of analgesics, psychiatric disorders, smoking, sleeping problems, a history of head and neck trauma and low educational level, but not with8|
  9. 9. caffeine use (Wiendels, 2006). In this study, the average intake of caffeine was7 consumptions a day, including coffee, tea, ice tea and cola. However, in alarge cross sectional study in Norway, high caffeine consumption (> 540 mg/d)was associated with increased prevalence of infrequent headache, whereaschronic headache was less likely among individuals with high caffeine consump-tion (Hagen, 2009). According to the authors these results may indicate thathigh caffeine consumption changes chronic headache into infrequent headachedue to the analgesic properties of caffeine, or that chronic headache suffererstend to avoid the intake of caffeine. This is in line with the conclusion of thereview by Shapiro (2008), stating that caffeine can exert potent pharmacologiceffects that can generate or alleviate headache, depending on the site of action,dosage and timing of exposure.5 Can you get a headache if you stop drinking coffee?Abrupt cessation of regular caffeine consumption may result in headacheamong sensitive individuals. The headache generally resolves within a few daysor at most one week after consumption stopped. In addition, the headachedisappears when caffeine consumption is resumed (Nehlig, 2004; Scher, 2004).Caffeine withdrawal headache are not experienced by all individuals; prevalencefigures vary between 0.4% and 50% (Shapiro, 2008). Caffeine withdrawal head-ache can be easily prevented by reducing caffeine consumption gradually in thedays before cessation of consumption, for instance in case of (religious) fastingor a surgical procedure. Coffee and the brain | 9
  10. 10. 6 Are fasting headaches related to caffeine consumption? Fasting of food is an important precipitating factor of headache and the probability of onset increases directly with the duration of fasting. Fasting headache is one of the most common forms of secondary headache, but much remains to be explained about the underlying patho-physiological mechanisms. Hypoglycemia (low blood glucose level) and caffeine withdrawal are suggested as potential triggers, although fasting headache may occur even when there is no hypoglycemia and in individuals who do not normally consume caffeine (Torelli, 2009). Headaches after fasting before and after surgical procedures are found to be related to habitual caffeine consumption (Nehlig, 2004). A study of prolonged fasting suggests that other factors like abstinence from water or foods, genetic background or cultural factors may contribute more strongly to fasting induced headache, but not fully exclude caffeine as a factor (Shapiro, 2008). 7 What is meant by weekend headache? Some people experience headaches in particularly on weekend mornings. Different explanations are proposed for this so called weekend headache (Couturier, 1992; Nehlig, 2004; Shapiro, 2004). It might be related to the change in stress level, or sudden disappearance of stress during the weekend. Change in the pattern of sleep, often longer than usual, has also been suggest- ed as an important cause. Other possible causes are increased consumption of alcohol at the beginning of the weekend, or missing breakfast because of sleep- ing late. Weekend headaches are also linked to a delay (sleep later) or avoidance of caffeine consumption during weekend mornings (see also question 5).10 |
  11. 11. Coffee intakeCaffeine is naturally present in coffee, tea and cocoa, and added in small quanti-ties to some soft drinks. Consumption of coffee varies largely between countries.In Europe the consumption of coffee ranges from 1.5 to 11.9 kg coffee perperson per year. The highest consumption occurs in Scandinavia (Finland 11.9kg coffee/person/year), and the lowest consumption in Poland (1.5 kg coffee/person/year) (International Coffee Organization, 2010).The amount of caffeine per cup of coffee varies with the type of coffee used(Arabica or Robusta), the brewing method (e.g. drip filter, instant, espresso,boiled) and the brewing strength (in the Netherlands on average 7 grams percup). The table on page 12 summarizes average values of caffeine per product.8 Can weekend headache be prevented and if yes how?If someone is prone to weekend headache, there are several steps to preventor diminish the headaches.• Identify triggers (see question 6 and 7) so these can be avoided.• In case of habitual caffeine consumption, include a cup of coffee for breakfast during the weekends.• Keep a regular schedule that includes a full night’s rest, balanced meals and exercise during the weekends (Harvard Health Publications, 2010). Coffee and the brain | 11
  12. 12. References • American Psychiatric Association (1994, 2000). Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV-TR) APA Press, Washington DC. • Anneken K e.a. (2010). Efficacy of fixed combinations of acetylsalicyclic acid, acetaminophen and caffeine in the treatment of idiopathic headache: a review. Eur J Neurol, 17: 534-540. • Armstrong LE e.a. (2007). Fluid, Electrolyte, and Renal Indices of Hydration During 11 Days of Controlled Caffeine Consumption. Int J Sport Nutr Exerc Met, 15: 252-265. • Couturier EGM (1992). Weekend attacks in migraine patients: caused by caffeine withdrawal? Cephalalgia, 12: 99-100. • Dutch Nutrition Center (2011), www.voedingscentrum.nl. • Hagen K e.a. (2009). High dietary caffeine consumption is associated with a modest increase in headache prevalence: results from the Head-HUNT Study. J Headache Pain, 10: 153-159. • Harvard Health Publications (2010). A Harvard Medical School Special Health Report. Headaches Relieving and preventing migraine and other headaches. • IHS - Headache Classification Subcommittee of the International Headache Society (2004). The International Classification of Headache Disorders. Cephalalgia, 24, S1: 1-160. • Institute of Medicine of National Academies; Food and Nutrition Board. Dietary Reference Intake for Water, Potassium, Sodium, Chloride and Sulfate. The National Academic Press (2004). www.nap.edu. • International Coffee Organization (2010). Monthly Coffee Market Report, Oct. 2010. www.ico.org. • Kolasa KM e.a. (2009). Hydration and Health Promotion. Nutrition Today, 44: 190-201. • Laska EM e.a. (1984). Caffeine as an analgesic adjuvant. JAMA 251: 1711-1718. • Nehlig A (2004). Caffeine and Headache: Relationship with the effects of caffeine on cerebral blood flow. In Nehlig A (ed) Coffee, Tea, Chocolate and the Brain; CRC Press LLC, Boca Raton, Florida: 175-186. • Nehlig A e.a. (2010). SPECT assessment of brain activation induced by caffeine: no effect on areas involved in dependence. Dialogues Clin Neurosci, 12: 255-263. • Olesen J and Steiner TJ (2004). The international classification of headache disorders, 2nd edn (ICDH-II). J Neurol Neurosurg Psychiatry, 75: 807-808. • Ruxton CHS (2008). The impact of caffeine on mood, cognitive function, performance and hydration: a review of benefits and risks. Nutr Bull, 33: 15-25. • Satel S (2006). Is caffeine addictive? A review of the literature. Am J Drug Alcohol Abuse, 32: 493-502. • Scher AI e.a. (2004). Caffeine as a risk factor for chronic daily headache. A population based study. Neurology, 63: 2022-2027. • Shapiro RE (2008). Caffeine and Headaches. Current Pain Headache Rep, 12: 311-315. • Torelli P e.a. (2009). Fasting Headache: A review of the literature and new hypotheses. Headache, 49: 744-752. • Wiendels NJ e.a. (2006). Chronic frequent headache in the general population: prevalence and associated factors. Cephalalgia, 26: 1434-1442. • World Health Organization (WHO, 1994). The ICD-10 classification of mental and behavioral disorders. WHO, Geneva. • Zhang WY e.a. (2001). A benefit-risk assessment of caffeine as an analgesic adjuvant. Drug Saf, 24: 1127-1142.14 |
  13. 13. 2 Coffee, caffeine and cognition1 What is cognitive function?The word ‘cognition’ comes from the Latin word ‘cognoscere’ which means‘to know’ or ‘to recognize’ (Nehlig, 2010). Cognitive function is a general termthat is used to describe a great variety of different brain mediated functions andprocesses. These brain functions allow us to perceive, evaluate, store, manipulateand use information from external sources, like our environment, and internalsources, like experience, memory and thoughts, and respond to that informa-tion (Schmitt, 2005). Cognitive functions can be clustered in six main domains:executive functions, memory functions, attention functions, perceptual functions,psychomotor functions and language skills (see schematic representation onpage 16). These distinct functions often act together to produce actual cogni-tive performance output. For example, efficient storage of new information inthe long-term memory cannot occur without proper attention for the relevantinformation, adequate perceptual processing, and the executive learning strate-gies. Besides, cognitive functioning is mediated by a number of other factorswhich are not considered to be cognitive functions themselves. A key mediator isthe level of central arousal, which can be roughly described as the level of mentalenergy. Mood state (sad, happy) is also known to modulate cognitive function, aswell as motivation and physical well-being. Coffee and the brain | 15
  14. 14. In doses normally consumed, caffeine blocks inhibitory A1 and A2A receptors,and hence increases central nervous system activity (Nehlig, 1992; Fredholm,1999; Daly, 2004; Fisone, 2004; Tieges, 2007).3 What is the effect of coffee or caffeine on alertness?It is well-known that caffeine ingestion leads to dose dependent increasedenergetic arousal, which reflects alertness and mental energy (Nehlig, 2010).However, the relationship between the level of arousal and task performance isnot a linear one, but follows an inverted U-curve: performance decrements canoccur due to under- and over-arousal (Schmitt, 2005). Furthermore, the optimalarousal level is thought to vary between different cognitive tasks (Van Boxtel,2004).Some of the most sensitive functions for increased arousal are reaction time andvigilance. There is a large number of scientific studies showing that consump-tion of caffeinated foods and beverages is associated with increased alertness,improvements of reaction time and vigilance performance. Most of this researchincludes computer tests which have the advantage of a standardized presenta-tion and accurate and detailed response capture. The level of performance isusually measured in terms of speed (e.g. simple reaction time) and accuracy(the amount of correct information), free recall of information or selective visualtasks. The stimulating effect of caffeine consumption on alertness and perform-ance efficiency was demonstrated for a variety of tasks (Lorist, 1994, 1996;Ruijter, 1999, 2000; Smit, 2000, 2005a; Smith, 2005b; Haskell, 2005; Hewlett,2007; Olson, 2010). EEG data support the stimulating effect of caffeine on thebrain (Lorist, 2003). Coffee and the brain | 17
  15. 15. How is caffeine metabolized in the body? After drinking a cup of coffee, caffeine is rapidly and efficiently absorbed from the gastro intestinal tract and peak plasma concentrations are reached between 15 and 120 minutes. Caffeine is distributed throughout the body and easily enters the brain. The half life of caffeine amounts 2.5 to 4.5 hours but can vary considerably depending on endogenous factors such as physiology and genet- ics, and exogenous factors such as lifestyle. For example, caffeine half-life can be reduced by about 50% in smokers compared to non-smokers. Caffeine is metabolized in the liver and its break down products are excreted through the kidney (Nehlig, 1992; Fredholm, 1999). 4 When is the effect of caffeine most noticeable? The impact of caffeine on increased alertness is more marked for individuals with low arousal levels. However, improved performance has also been observed when reduced alertness is not involved (Smith, 2002; Snel, 2004). Sleepiness leads to deterioration in performance and is associated with an increased risk of error and injury. For instance shift work is a major cause of sleepiness as it requires being awake at times which are different from those dictated by our body-clock. A review of 13 trials shows that caffeine can reduce the number of errors and improve cognitive performance in shift workers and also in persons suffering from jet lag (Ker, 2010). In addition, caffeine or coffee consump- tion has been shown to counter-act fatigue induced by a night with sleep- deprivation (Lorist, 1994), and to reduce the post lunch dip (Robelin, 1998), to improve nocturnal driving performance whereas napping did not (Sagaspe, 2007) and is associated with improved alertness and reduced risk for accidents at work (Smith, 2005a).18 |
  16. 16. In the same way, for short stopovers (1-2 days) during trips with time zonedifferences, judicious naps combined with caffeine and short-term hypnoticsappear to be the best way to maintain alertness and sleep (Arendt, 2009).5 How much coffee do I have to drink to become more alert and achieve a better performance?The benefit of caffeine in typical servings of coffee (60-100 mg of caffeine) onalertness was demonstrated in several studies. Even lower doses have beendemonstrated to increase alertness, such as 40 mg caffeine per serving (Smit,2000), 32 mg per serving (Lieberman, 2001) or doses as low as 12.5 mgcaffeine (Smit, 2000). However, the effect of low doses of caffeine was observedpredominantly in those people who are not accustomed to taking caffeine.Higher caffeine intakes, as those found in more than one or two cups ofcoffee do not necessarily result in additional increases in alertness (Smit, 2000;Quinlan, 2000). It is thought that the relationship between the level of arousaland task performance follows an inverted U-curve: performance decrementscan occur due to under- and over-arousal (Schmitt, 2005). In general, beneficialbehavioral effects of caffeine are found with doses comparable to those found inhabitual coffee consumption levels (Smith, 2002). Coffee and the brain | 19
  17. 17. 6 How can drinking coffee contribute to attention and concentration? Concentration is usually related with improved selective attention, meaning that the mind is focusing narrowly on the task at hand. Focusing of attention can be improved by caffeine as shown in several selective attention task studies. Subjects had to focus on the task and neglect distracters. The results suggested an increased performance in selection of relevant information (Smith, 1999; Ruijter, 2000; Lorist, 2003; Snel, 2004). Recently caffeine was shown to improve participant’s ability to efficiently use stored information and inhibit the influence of action-irrelevant information (Brunyé, 2010). 7 What is the effect of coffee or caffeine on memory? Memory is one aspect of cognition which includes encoding, consolidation and retrieval of information. Memory can be divided according to the duration of memory: short-term memory, which is transient and limited in capacity and long-term memory, which includes the vast store of knowledge and the record of prior events, for potentially unlimited duration. Working-memory refers to short-term memory and other processing mechanisms that are assumed to be necessary in order to keep things in mind while performing complex tasks such as reasoning, comprehension and learning. Memory is not located in a single part of the brain, but involves a widely distributed network located in different brain structures (Cowan, 2008; Baddeley, 2010). Low doses of caffeine enhance working memory performance, while higher doses are found to decrease it, possibly due to over-stimulation. Comparable results are shown in a study with low-load memory tasks versus high load memory tasks (Nehlig, 2010). Caffeine was shown to facilitate low-difficulty performance in low load memory tasks. High-load and complicated tasks20 |
  18. 18. induced increased arousal by itself, and caffeine could lead to over-arousal.Thus caffeine appears to rather improve working memory performance underconditions that otherwise produce low arousal. There are not many studieson the effects of caffeine on long-term memory. In elderly caffeine could helpattenuating age-related arousal decrements to reduce the decline in memoryperformance during the day (Ryan, 2002; Nehlig, 2010). However, the effects ofcaffeine on memory are inconsistent. Discrepancies between studies may be dueto the memory assessment method (recall or recognition), time frame (immedi-ate versus delayed), sex and age of the subjects.8 Does caffeine have a real impact on cognitive functioning, or does it just alleviate withdrawal symptoms, in other words, restore cognitive functioning to baseline levels?It has been suggested that the positive effects of caffeine really reflect removalor negative effects of caffeine withdrawal (James, 2005). However, this viewcannot account for effects observed in non-consumers or deprived individuals(Smith, 2002). Several studies suggested a real impact of caffeine on mood andperformance, irrespective of an overnight caffeine withdrawal. No difference inmood and performance has been shown between habitual caffeine consumersafter an overnight caffeine withdrawal and non-caffeine consumers. Moreover,caffeine challenge enhanced mood and performance and the effects increasedwith the caffeine dose (Haskell, 2005; Smith, 2005b, 2006). Further, a studyof the effects of caffeine following a day of normal consumption showed thatcaffeine had similar effects in those who had abstained from caffeine for morethan 6 hours and those who had consumed caffeine up to the time of testing(Hewlett, 2007). Coffee and the brain | 21
  19. 19. 9 Can a cup of coffee affect my mood? Enjoying a cup of coffee for its taste and smell, talking with family, friends or colleagues during a coffee break might be part of the benefit coffee can have on our mood. Mood states are generally assessed using validated self-rating scales with a vari- ety of mood terms like happy, sad, depressed, pleasant, calm and contented.22 |
  20. 20. Despite the variability in mood definitions, research has provided a fairly consist-ent picture of effects of caffeine on mood state. In low to moderate dosages(20-200 mg), caffeine has been quite constantly shown to improve mood state(Smith, 2004; Casas, 2004; Smith, 2005b; Olson, 2010). People report thatthey feel energetic, imaginative, efficient, self confident and alert after caffeineconsumption. They feel more able to concentrate and motivated to work butalso more willing to socialize (Fredholm, 1999). In a recent prospective followup study coffee consumption was associated with a decreased risk of depression(Ruusunen, 2010).10 Can caffeine consumption cause anxiety?In general it appears that low doses of caffeine tend to improve the mood statesand that high caffeine doses are associated with negative affective change, likerestlessness and jitteriness. Individual differences in caffeine sensitivity very likelyplay a substantial role in determining the mental and physical response tocaffeine (Smith, 2004). In addition, a genetic variation on the adenosinereceptor A2A is associated with sensitivity to caffeine effects on anxiety (Alsene,2003).Anxiety is rarely seen with the average range of caffeine consumption, butthe literature suggests that extremely high doses of caffeine may increaseanxiety (Smith, 2002). Moreover, caffeine is a substance that is normallyconsidered as ‘self-regulating’, meaning that most people know when they tookenough coffee and usually stop drinking before negative effects will emerge(Tieges, 2007). Coffee and the brain | 23
  21. 21. 11 Can caffeine/coffee consumption interfere with sleep? Caffeine can increase wakefulness and has been shown to counter-act fatigue induced by a night with sleep-deprivation (see also question 4). In a French study on sleep duration and caffeine consumption in a middle aged working population no effect on sleep duration was found up to a habitual use of 7 cups of coffee or 600 mg of caffeine equivalent (Sanchez-Ortuno, 2005). Regular consumption of caffeine can result in some degree of tolerance, reducing the effects on sleep (Bonnet, 2005). Other research indicated that drinking caffeinated beverages in the evening may interfere with the onset of sleep in caffeine sensitive subjects. Differences in caffeine pharmacokinetics have been reported for sleep sensitive and non-sensitive subjects (Bchir, 2006). Caffeine elimination was slower in subjects with sleep disturbances; they had half lives for caffeine between 6.5 and 8 hours. The average half life for caffeine amounts 2.5 to 4.5 hours (see frame on page 18). Significant plasma caffeine concentrations may persist during the night when caffeine is consumed in the late afternoon. In addition, a genetic variation on the adenosine receptor A2A is associated with caffeine sleep sensitivity and a habitual caffeine consumption (Cornelis, 2007; Retey, 2007). In case of insomnia caffeine abstinence or avoiding caffeine consumption in the afternoon and evening might be one of the factors to consider, next to regular exercise, sleeping in a quiet and comfortable environment and avoiding TV watching in the bedroom and strenuous activities shortly before going to bed.24 |
  22. 22. Is it safe to consume caffeine?Caffeine is one of the most investigated components in our diet. Based onextensive reviews of scientific literature there is general consensus that 400mg caffeine per day (about 4-5 cups of coffee) are not associated with adversehealth effects in adults. Women who are pregnant, lactating or planning tobecome pregnant are recommended to limit their caffeine consumption to200-300 mg per day (about 2-3 cups of coffee). Caffeine intake in childrenshould be limited to 2.5 mg caffeine per kg bodyweight per day (Nawrot,2003; Higdon, 2006; Fredholm, 1999). Coffee and the brain | 25
  23. 23. References • Alsene K e.a. (2003). Association between A2a receptor gene polymorphisms and caffeine-induced anxiety. Neuropsychopharmacology, 28(9): 1694-702. • Arendt (2009). Managing jet lag: Some of the problems and possible new solutions. Sleep Med Rev, 13(4): 249-56. • Baddeley A (2010). Working memory. Curr Biol, 20(4): R136-140. • Bchir F e.a. (2006). Differences in pharmacokinetics and electroencephalographic responses to caffeine in sleep-sensitive and non-sensitive subjects. CR Biologies, 329: 512-519. • Bonnet MH e.a. (2005). The use of stimulants to modify performance during sleep loss: A review by the Sleep Deprivation and Stimulant Task Force of the American Academy of Sleep Medicine. Sleep, 28(9): 1163-1187. • Brunyé TT e.a. (2010). Caffeine modulates attention network function. Brain and Cognition, 72(2): 181-189. • Casas M (2004). Effects of Coffee and Caffeine on Mood and Mood Disorders. In Nehlig A (ed) Coffee, Tea, Chocolate and the Brain; CRC Press LLC, Boca Raton, Florida: 73-83. • Cornelis MC e.a. (2007). Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Am J Clin Nutr, 86: 240–244. • Cowan N (2008). What are the differences between long-term, short-term, and working memory? Prog Brain Res, 169: 323-338. • Daly JW e.a. (2004). Mechanism of Action of Caffeine on the Nervous System. In Nehlig A (ed) Coffee, Tea, Chocolate and the Brain; CRC Press LLC, Boca Raton, Florida: 1-11. • Fisone G e.a. (2004). Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci, 61(7-8): 857-872. • Fredholm B e.a. (1999). Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacology Rev, 51(1): 83-133. • Haskell CF e.a. (2005). Cognitive and mood improvements of caffeine in habitual consumers and habitual non-consumers of caffeine. Psychopharmacology, 179: 813-825. • Hewlett P and Smith A (2007). Effects of repeated doses of caffeine on performance and alertness: new data and secondary analyses. Hum Psychopharmacology, 21: 167-180. • Higdon JV and Frei B (2006). Coffee and health: a review of recent human research. Critical Reviews in Foods Science and Nutrition, 56(2): 101-123. • James JE and Rogers PJ (2005). Effects of caffeine on performance and mood: withdrawal reversal is most plausible explanation. Psychopharmacology, 182: 1-8. • Ker K e.a. (2010). Caffeine for the prevention of injuries and errors in shift workers (Review). The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. www.thecochranelibrary. • Lieberman HR (2001). The effects of Ginseng, Ephedrine, and Caffeine on cognitive performance, mood and energy. Nutrition Reviews, 59: 91-102. • Lorist MM and Tops M (2003). Caffeine, fatigue and cognition. Brain and Cognition, 53: 82-84. • Lorist MM e.a. (1994). Influence of caffeine on information processing stages in well rested and fatigued subjects. Psychopharmacology, 113: 411–421. • Lorist MM e.a. (1996). Acute effects of caffeine on selective attention and visual search processes. Psychophysiology, 33: 354-361. • Nawrot P e.a. (2003). Effects of caffeine on health. Food Additives and Contaminants, 20(1): 1-30. • Nehlig A e.a. (1992). Caffeine and the central nervous system: Mechanisms of action, biochemical, metabolic, and psycho stimulant effects. Brain Research Reviews, 17: 139-170. • Nehlig A (2010). Is Caffeine a Cognitive Enhancer? J Alzheimers Dis, 20, S1: 85-94.26 |
  24. 24. • Olson CA e.a. (2010). Effects of Adenosine Antagonists, Quercetin and Caffeine, on Vigilance and Mood. J Clin Psychopharmacology, 30(5): 537-578.• Quinlan PT e.a. (2000). The acute physiological and mood effects of tea and coffee: the role of caf- feine level. Pharmacol Biochem Behav, 66(1): 19-28.• Retey JV e.a. (2007). A genetic variation in the adenosine A2A receptor gene (ADORA2A) contributes to individual sensitivity to caffeine effects on sleep. Clin Pharmacol Ther, 81: 692–698.• Robelin M and Rogers PJ (1998). Mood and psychomotor performance effects of the first, but not of subsequent, cup of coffee equivalent doses of caffeine consumed after overnight caffeine abstinence. Behav Pharmacol, 9(7): 611-618.• Ruijter J (1999). The influence of different doses of caffeine on visual task performance. Journal of Psychophysiology, 13: 37-48.• Ruijter J e.a. (2000). The effects of caffeine on visual selective attention to color: An ERP study. Psychophysiology, 37: 427-439.• Ruusunen A e.a. (2010). Coffee, tea and caffeine intake and the risk of severe depression in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Public Health Nutrition, 1-6.• Ryan L e.a. (2002). Caffeine reduces time-of-day effects on memory performance in older adults. Psychological Science, 13: 68-71.• Sagaspe P (2007). Aging and nocturnal driving: better with coffee or a nap? A randomized study. Sleep, 30(12): 1808-1813.• Sanchez-Ortuno M e.a. (2005). Sleep duration and caffeine consumption in a French middle-aged working population. Sleep Medicine, 6: 247-251.• Schmitt JAJ e.a. (2005). General methodological considerations for the assessment of nutritional influences on human cognitive functions. Eur J Nutr, 44: 459-464.• Smit HR and Rogers PJ (2000). Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers. Psychophymacology, 152: 167-173.• Smith A (2002). Effects of caffeine on human behaviour. Food and Chemical Toxicology, 40:1243-1255.• Smith AP e.a. (1993). Investigation of the Effects of Coffee on Alertness and Performance during the day and night. Neuropsychobiology, 27: 217-223.• Smith AP e.a. (1999). Effects of low dose of caffeine given in different drinks on mood and performance. Human Psychopharm Clin Exp, 14: 473-482.• Smith AP (2005a). Caffeine at work. Hum Psychopharmacol. 20(6): 441-445.• Smith AP e.a. (2005b). Effects of repeated doses of caffeine and mood and performance of alert and fatigued volunteers. J Psychopharmacol, 19(6): 620-626.• Smith AP e.a. (2006). Effects of caffeine in overnight withdrawn consumers and non-consumers. Nutritional Neuroscience, 9: 63-71.• Smith BD e.a. (2004). Arousal and behaviour: Biopsychological Effects of Caffeine. In A. Nehlig (ed). Coffee, Tea, Chocolate, and the Brain; CRC Press LLC, Boca Raton, Florida: 35-52.• Snel J e.a. (2004). Coffee, Caffeine, and Cognitive Performance. In A. Nehlig (Ed.). Coffee, Tea, Chocolate, and the Brain. Boca Raton, FL: CRC Press: 53-71.• Tieges Z (2007). Caffeine and cognitive control: Behavioural and electrophysiological studies. Thesis: ISBN 987-90-9022340-7.• Van Boxtel MPJ and Schmitt JAJ (2004). Age-Related Changes in the Effects of Coffee on Memory and Cognitive Performance. In Nehlig A (ed) Coffee, Tea, Chocolate and the Brain; CRC Press LLC, Boca Raton, Florida: 85-96. Coffee and the brain | 27
  25. 25. 28 |
  26. 26. 3 Coffee and cognitive aging1 What is the difference between normal cognitive decline, mild cognitive impairment (MCI) and dementia?By late adulthood, people typically experience some deterioration in cogni-tive abilities as part of the normal course of aging. Abilities, such as memory,reasoning and processing speed, all seem to decline, on average, with age(Corley, 2010). People with mild cognitive impairment (MCI) suffer from moresevere memory impairments beyond that would be expected according to age(Roberts, 2009). People with MCI are at higher risk of progressing to dementiaand Alzheimer’s disease, which in turn is the leading cause of dementia. Withdementia, people lose their cognitive abilities to an extent that they are unableto carry out normal activities and relationships. In addition to memory lossesalso behavior and personality changes can occur.2 What are the acute effects of coffee in elderly people?It’s well known that caffeine ingestion leads to dose dependent increased ener-getic arousal, which reflects alertness and mental energy (Nehlig, 2010). Caffeineis a mild stimulant and its cognitive enhancing effects are more pronounced inindividuals with low arousal levels, for instance due to sleep deprivation, fatigue orprolonged mental activity (see chapter 2, questions 3 and 4). Since mental energyand speed of information processing diminish with age, elderly in particular couldbenefit from the cognitive effects of caffeine. The vast majority of knowledge onthe acute behavioral effects of caffeine is based on experiments with young ormiddle-aged subjects. Although caffeine appears to be metabolized similarly inyoung and old individuals, only few studies have investigated the acute cognitiveeffects of caffeine in elderly. The results indicate that caffeine may restore arousal Coffee and the brain | 29
  27. 27. levels and hence facilitate cognitive functioning (Van Boxtel, 2004). This effect is even more pronounced in situations of prolonged mental activity, since elderly have less compensatory capacity (spare energy sources). Moreover, research suggests that caffeine intake can ameliorate the decline in memory performance during the day in older adults (Ryan, 2002). There is some, although very limited, evidence suggesting that older people may benefit more from relatively higher dosage (Van Boxtel, 2004). It is suggested to be an interesting topic for further research since caffeine intake typically increases in early adulthood and declines with older age. 3 Could caffeine counteract age-related cognitive decline? There is a growing number of epidemiological studies suggesting that coffee consumption is associated with better cognitive performance later in life. In a large cross- sectional study of 9,003 British adults a dose-response trend between habitual coffee consumption and cognitive abilities was measured; the oldest men and women seemed to benefit most from a higher caffeine in- take (Jarvis, 1993). Higher caffeine intake was not associated to better cognition after 6 years in 1,376 individuals studied in the Netherlands (Van Boxtel, 2003). In a prospective population study in France, higher caffeine consumption was associated with less memory decline in women but not in men. The association was stronger with increasing age and higher caffeine doses (> 300 mg per day) (Ritchie, 2007). Similar results were found in a study by Johnson-Kozlow (2002). In a longitudinal prospective cohort study with 676 older men in Finland, Italy and the Netherlands, coffee intake was associated with lower levels of cognitive decline 10 years later in life, with 4.3 times less decline in men consuming 3 cups a day in comparison with non-consumers (Van Gelder, 2007).30 |
  28. 28. In a Scottish study, a general trend was shown for individuals who drink morecoffee and less tea to have better cognitive health at age 70 (Corley, 2010). Sofar, results indicate that habitual coffee and or caffeine intake seems to be as-sociated with less cognitive decline in elderly.4 Does caffeine intake protect from dementia and Alzheimer’s disease?There are currently no cures and only limited treatment options for Alzheimer’sdisease. Research focused on prevention of Alzheimer disease suggested thatcoffee and caffeine might have a protective effect on the likelihood of develop-ing Alzheimers’s disease (Rosso, 2008). In a meta-analysis of two case-controlstudies and two cohort studies on coffee consumption and the risk of Alzhe-imer’s disease a protective effect of coffee consumption was found (BarrancoQuintana, 2007). In the pooled estimate the risk was 0.73 (i.e. 27% lower) forcoffee-users versus non-coffee users. In a Finnish cohort study with an averagefollow-up of 21 years, coffee drinking at midlife was associated with a decreasedrisk of dementia and Alzheimer’s disease and dementia later in life. There areseveral indications that caffeine, and perhaps other components in coffee aswell, play a neuroprotective role in the aging brain through a combination ofactions, including anti-inflammatory effects by blockade of both A1 and A2Areceptors. Caffeine has been suggested to increase transcription factors whichenhance cell proliferation and prevent cell death. Moreover, caffeine has beenshown to reduce the negative effects of ␤-amyloid, whose accumulation is thepathological signature of Alzheimer disease (Rosso, 2008). Caffeine consump-tion was shown to be dose-dependently related with less white matter lesions inelderly women, which is an indication of less ␤-amyloid accumulation (Ritchie,2010). These biological findings indicate that the relationship between caffeineand cognitive decline found in epidemiological research is highly likely to be atrue causal relationship and not a spurious association (Ritchie, 2010). Coffee and the brain | 31
  29. 29. Polyphenols in coffee have been hypothesized to neutralize free radicals that can cause damage to neurons and other cells and have also anti-inflammatory prop- erties. There are still a lot of questions to be answered before a conclusion on the potential protective effect of coffee and or caffeine can be drawn, however the results so far are encouraging. 5 What causes Parkinson’s disease and what is the effect of coffee? Parkinson’s disease is suggested to be a multifactorial disease, although the precise cause for Parkinson’s disease remains still undetermined. Complex interactions between neurotoxins and neuroprotective agents with genetic factors are thought to be responsible for the development and progression of the disease (Morelli, 2010). Genetic factors seem to be important in early-onset cases of Parkinson’s disease, while environmental and lifestyle factors are probably more relevant in the development of Parkinson’s disease at older ages (Costa, 2010). Among these lifestyle factors, coffee/caffeine is of particular interest in light of caffeine’s safety and widespread consumption. Caffeine has been demonstrated to be neuropro- tective in various experimental models of Parkinson’s disease (Xu, 2010; Morelli, 2010; Kachroo, 2010), probably via blocking A2A receptors in the brain. The knowledge on the plausible biological mechanism based on the pharmacological actions of caffeine strengthens the inverse association between coffee drinking and Parkinson’s disease found in epidemiological research (Costa, 2010).32 |
  30. 30. 6 Is coffee consumption a protective factor for Parkinson’s disease?The first study to indicate the possible effects of drinking coffee and reducingthe risk of Parkinson disease was published as early as 1968 (Nefzger, 1968).More than 30 years later, a meta-analysis including 8 case-control and 5 cohortstudies demonstrated that the relative risk of Parkinson’s disease was 30% lowerfor coffee drinkers, in comparison to non-coffee drinkers (Hernan, 2002).A recent systemic review and meta-analysis of 26 studies (7 cohorts, 2 nestedcase-controls, 16 case-controls and 1 cross-sectional study) on caffeine andthe risk of Parkinson’s disease confirmed the strength of the inverse association(Costa, 2010). A 25% reduction in risk of Parkinson’s disease among caffeineconsumers was demonstrated. The results also indicate a linear dose-responserelation, with higher intakes of caffeine being associated with lower risk ofParkinson’s disease. Moreover, coffee consumption is significantly associatedwith a reduced Parkinson’s disease mortality in men (Ascherio, 2004); the effectin women was dependent on post menopausal estrogens use. In womenconsuming 4 cups or more coffee per day compared to women not consum-ing coffee the risk reduced by 53% among never users and increased by 30%among users (Ascherio, 2004). These differences could partly reflect a varia-tion in the genetic expression of one enzyme metabolizing caffeine, CYP1A2rs762551 (Palacios, 2010). Coffee and the brain | 33
  31. 31. References • Ascherio A e.a. (2004). Coffee consumption, Gender, and Parkinsons’s disease mortality in the Can- cer prevention Study II Cohort: The Modifying Effects of Estrogen. Am J Epidemiol 160(10): 977-984. • Barranco Quintana JL e.a. (2007). Alzheimer’s disease and coffee: a quantitative review. Neurol Res, 29: 91-95. • Corley J e.a. (2010). Caffeine consumption and cognitive function at age 70: The Lothian Birth Cohort 1936 Study. Psychosom Med, 72: 206-214. • Costa J e.a. (2010). Caffeine Exposure and the Risk of Parkinson’s Disease: A Systemic Review and Meta-Analysis of Observational Studies, 20: S221-S238. • Hernan MA (2002). A meta-analysis of Coffee Drinking, Cigarette Smoking, and the Risk of Parkinson’s Disease. Ann Neurol, 52: 276-284. • Jarvis MJ (1993). Does caffeine intake enhance absolute levels of cognitive performance? Psychopharmacology, 110(1-2): 45-52. • Johnson-Kozlow M e.a. (2002). Coffee consumption and cognitive function among older adults. Am J Epidemiol, 156: 842-850. • Kachroo A e.a. (2010). Caffeine protects against combined paraquat and maneb-induced dopaminergic neuron degeneration. Exp Neurol, 223: 657-661. • Morelli M and Simola N (2010). Can dietary substances protect against Parkinson’s disease? The case of caffeine. Exp Neurol, 225(2): 246-249. • Nefzger MD e.a. (1968). A retrospective study of smoking in Parkinson’s disease. Am J Eidemiol, 88: 149-158. • Nehlig A (2010). Is Caffeine a Cognitive Enhancer? J Alzheimer’s Disease 20, S1: 85-94. • Palacios N e.a. (2010). Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinsons disease in men and women. Parkinsonism Relat Disord, 16(6): 370-375. • Ritchie K e.a. (2007). The neuroprotective effects of caffeine. A prospective population study. Neurology, 69: 536-545. • Ritchie K e.a. (2010). Caffeine, cognitive functioning, and white matter lesions in the elderly: establishing causality from epidemiological evidence. J Alzheimers Dis, 20 S1: 161-166. • Roberts JL e.a. (2009). Subject memory Complaints and Awareness of Memory Functioning in Mild Cognitive Impairment: A Systematic Review. Demet Geriatr Cogn Disord, 28: 95-109. • Rosso A e.a. (2008). Caffeine: Neuroprotective Functions in Cognition and Alzheimer’s Disease. Am J Alzheimers Dis Other Dem, 23(5): 417-422. • Ryan L e.a. (2002). Caffeine reduces time-of-day effects on memory performance in older adults. Psychological Science, 13(1): 68-71. • Van Boxtel MPJ e.a. (2003). The effects of habitual caffeine use on cognitive change: a longitudinal perspective. Pharmacol Biochem Behav, 75: 921-927. • Van Boxtel MPJ and Schmitt JAJ (2004). Age-Related Changes in the Effects of Coffee on Memory and Cognitive Performance. In Nehlig A (ed) Coffee, Tea, Chocolate and the Brain; CRC Press LLC, Boca Raton, Florida: 85-96. • Van Gelder B e.a. (2007). Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study. Eur J Clin Nutr, 61(2): 226-232. • Xu K e.a. (2010). Neuroprotection by caffeine: Time course and role of its metabolites in the MPTP model of Parkinson Disease. Neuroscience, 167(2): 475-481.34 |
  32. 32. Study of coffee and healthEvery type of research has its own evidential value and limitations.Most of the studies reported in this brochure can be differentiated into:1. Meta-analysis: A literature study of various studies (intervention studies, cohort studies and/or patient control studies) of the relationship between coffee con- sumption behaviour and a biomarker or (medical) condition, with the aim of obtaining a more precise outcome.2. Cohort study (prospective): In this brochure in the case of this type of study large groups of people have been monitored (prospectively) over a longer period. In this context at the start of the study differences in coffee consumption between people who have and have not developed a (medical) condition during the study are examined. The pattern of coffee consumption of the participants has therefore not been influenced by the condition.3. Cross-sectional study: This is a study in which one monitors simultaneously (smaller) cohorts which follow each other in time. For example a group in the age range 31-45 and a group in the age range 45-60 are then examined simul- taneously. In this case at the start of the study differences in coffee consumption have been examined between people who did and people who did not acquire the (medical) condition during the study. In this manner a good picture can be obtained of the association between for example coffee consumption and the development of a condition between the ages of 30 and 60.4. Patient-control study: In the case of this type of study the differences in coffee consumption patterns are investigated in groups of people who have and have not developed the (medical) condition. In this case therefore questions are asked after the event about previous coffee consumption behaviour. A disad- vantage of this type of study may be that the coffee consumption pattern of the people who have that condition has been modified or is assessed differently than in the case of people who do not have the condition.5. Intervention study: In the case of this type the effect of the substance to be investigated on a group of people is measured and compared with a control group, which is not given the substance. Intervention studies in the area of coffee research are usually relatively short and the group size is limited. Coffee and the brain | 35
  33. 33. Coffee brain and the KO F F I E E N G E Z O N D H E I D www.koffieengezondheid.nl

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