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Coffee, Caffeine and Blood Pressure: a Critical Review

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Coffee, Caffeine and Blood Pressure: a Critical Review European Journal of Clinical Nutrition (1999) 53, 831±839 ß 1999 Stockton Press. All rights reserved 0954±3007/99 $15.00 http://www.stockton-press.co.uk/ejcn Coffee, caffeine and blood pressure: a critical review M-L Nurminen1*, L Niittynen2, R Korpela2 and H Vapaatalo1 1Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland; and 2Valio Ltd, Research and Development Centre, Helsinki, Finland Objective: We review the published data relating to intake of coffee and caffeine on blood pressure in man. We also refer to studies on the possible mechanisms of actions of these effects of caffeine. Design: The MEDLINE and Current Contents databases were searched from 1966 to April 1999 using the text words `coffee or caffeine' and `blood pressure or hypertension'. Controlled clinical and epidemiologic studies on the blood pressure effects of coffee or caffeine are reviewed. We also refer to studies on the possible mechanisms of action of these effects of caffeine. Results: Acute intake of coffee and caffeine increases blood pressure. Caffeine is probably the main active component in coffee. The pressor response is strongest in hypertensive subjects. Some studies with repeated administration of caffeine showed a persistent pressor effect, whereas in others chronic caffeine ingestion did not increase blood pressure. Epidemiologic studies have produced contradictory ®ndings regarding the association between blood pressure and coffee consumption. During regular use tolerance to the cardiovascular responses develops in some people, and therefore no systematic elevation of blood pressure in long-term and in population studies can be shown. Conclusions: We conclude that regular coffee may be harmful to some hypertension-prone subjects. The hemodynamic effects of chronic coffee and caffeine consumption have not been suf®ciently studied. The possible mechanisms of the cardiovascular effects of caffeine include the blocking of adenosine receptors and the inhibition of phosphodiesterases. Descriptors: coffee; caffeine; blood pressure; hypertension; adenosine receptors; phosphodiesterases Introduction Benowitz, 1994). Caffeine produces a variety of adverse effects, including gastrointestinal disturbances, tremor, Coffee is one of the most widely used non-alcoholic headache and insomnia (Chou & Benowitz, 1994). It can beverages in industrialized countries. Caffeine is an impor- also induce palpitations and sometimes even cardiac tant component of this drink: a 150 ml cup of coffee arrhythmias (Mehta et al, 1997), and it has been suggested contains about 60 ± 120 mg of caffeine (Barone & Roberts, that caffeine may be potentially hypertensive (James 1997; 1996). Other common dietary sources of caffeine are tea Jee et al, 1999). and cola soft drinks. The caffeine content in tea is aproxi- Caffeine is readily absorbed from the gastrointestinal mately 20 ± 40 mg per 150 ml cup, and that of cola soft tract and rapidly distributed in all the body ¯uids (Chou & drinks ranges from 15 to 24 mg per 180 ml serving. The Benowitz, 1994). There is, however, considerable inter- consumption of coffee in Nordic countries is among the individual variability in the rate of absorption. The peak highest in the world; for instance, in Denmark the mean plasma concentrations of caffeine are usually obtained daily caffeine intake is approximately 7 mg=kg (Barone & within 30 ± 120 min of oral intake (Robertson et al, 1978; Roberts, 1996). In addition, caffeine is used as an adjuvant Smits et al, 1985, 1986a). Caffeine is extensively metabo- in many prescription and over-the-counter drugs, e.g. in lized in the liver via a complex set of reactions. The combination with nonsteroidal anti-in¯ammatory drugs in primary pathway is oxidative N-demethylation to para- analgesic formulations and with ergotamine in drugs for xanthine, theobromine, theophylline and direct ring oxida- treating migraine (Chou & Benowitz, 1994). Combination tion to 1,3,7-trimethyluric acid (Tang-Liu et al, 1983). The of caffeine and ephedrine has also been reported to reduce elimination half-life of caffeine in man ranges from 2 ± weight in obese subjects, whereas both substances given 10 h, with a mean of about 4 ± 5 h (Robertson et al, 1981; alone had no effect (Astrup et al, 1992). Tang-Liu et al, 1983; Smits et al, 1985). A dose-dependent Caffeine exerts a variety of stimulatory effects upon the pharmacokinetics may occur, which means that enzymes central nervous system, and it is probably the most widely involved in metabolism become saturated (Tang-Liu et al, used psychoactive substance. It also increases the respira- 1983). The metabolism is slowed during pregnancy (Knutti tory rate and causes bronchodilatation, stimulates lipolysis, et al, 1981) and in women taking oral contraceptives and increases diuresis (Robertson et al, 1978; Chou & (Callahan et al, 1983). On the other hand, the clearance rate of caffeine is greater in smokers than in non-smokers *Correspondence: M-L Nurminen, Institute of Biomedicine, Department (Parsons & Neims, 1978). of Pharmacology and Toxicology, PO Box 8, FIN-00014 University of Coffee and other caffeine-containing beverages are Helsinki, Finland. E-mail: marja-leena.nurminen@helsinki.®. widely consumed on a daily basis. It is therefore important Guarantor: M-L Nurminen. to de®ne the possible risks and bene®ts associated with Contributors: L Niittynen wrote the chapter dealing with acute intake of caffeine intake, in order to be able to better inform coffee and caffeine, R Korpela and H Vapaatalo wrote the chapter dealing with the mechanisms and M-L Nurminen is responsible for the other parts both health professionals and the public. The possible of the manuscript. association between coffee consumption and increased Coffee, caffeine and blood pressure M-L Nurminen et al 832 risk of coronary heart disease has been debated for decades intake on blood pressure (Table 1). However, the results without any clear agreement of causal relation (Wilson et have remained inconsistent. Some of these studies found al, 1989; Greenland, 1993; Chou & Benowitz, 1994; that habitual consumption of coffee or caffeine was asso- Kawachi et al, 1994; Thompson, 1994). Possible risk ciated with slightly elevated blood pressure (Lang et al, factors predisposing consumers to caffeine-induced coron- 1983a, b; Birkett & Logan, 1988; LoÈwik et al, 1991; Burke ary heart disease may include blood pressure and plasma et al, 1992; Narkiewicz et al, 1995). However, many of the cholesterol levels elevated by coffee. epidemiologic studies showed no relation (Shirlow et al, The objective of this overview is to summarize current 1988; Wilson et al, 1989; HoÈfer & BaÈttig, 1993; Lewis et knowledge of the effects of coffee and caffeine intake on al, 1993), and some even showed a small inverse associa- blood pressure. The possible mechanisms of these tion between self-reported coffee consumption and blood responses will also be discussed. The relation between pressure (Periti et al, 1987; Stensvold et al, 1989; Salvag- coffee consumption and plasma lipids has been reviewed gio et al, 1990; Gyntelberg et al, 1995; Wakabayashi et al, elsewhere (Thelle et al, 1987; Pirich et al, 1993, Thomp- 1998). Consumption of coffee appears to be positively son, 1994) and is therefore not included in this article.SBP, associated with an increased risk of thromboembolic systolic blood pressure; DBP, diastolic blood pressure. stroke in middle-aged hypertensive men (Hakim et al, 1998). Methods Development of tolerance during habitual use may The MEDLINE and the Current Contents literature explain why coffee consumption in some epidemiologic searches for published articles in English from January studies did not appear to have a clear effect on blood 1966 to April 1999 were carried out using the keywords pressure. However, a large cross-sectional study with over `coffee or caffeine' and `blood pressure or hypertension'. 5000 participants found that caffeine consumption within Articles concerning human epidemiological and controlled the last 3 h was associated with signi®cantly higher blood clinical studies that have relevant data on the effects of pressure than when caffeine was not consumed in the last coffee or caffeine on blood pressure were included in the 9 h (Shirlow et al, 1988). A smaller study with 338 female present review. In addition, reference lists were reviewed to subjects also con®rmed that recent coffee consumption was obtain applicable articles. We also referred to animal and in related to increased blood pressure (HoÈfer & BaÈttig, 1993). vitro studies that dealt with the possible mechanisms of In some of the epidemiologic studies blood pressure mea- actions of the cardiovascular effects of coffee or caffeine. surements were taken under conditions when fasting was The inclusion criteria for clinical trials were a controlled required from the participants (Salvaggio et al, 1990; Lewis study design and random assignment. Exclusion criteria et al, 1993; Gyntelberg et al, 1995). This may have led to were an open study design, the numerical values of the an underestimation of the blood pressure levels in the blood pressure not given or statistical analysis not per- studies with negative results, because caffeine deprivation formed. has been associated with lower blood pressure in habitual consumers (James, 1994; Phillips-Bute & Lane, 1998). Epidemiologic studies on coffee and blood pressure Thus, the inverse association between coffee intake and Several cross-sectional
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