By: Harshal Patil MDa, Carl J Lavie MDb, James H O'Keefe MDa
Published in Missouri Medicine, the journal of the Missouri State Medical Association, November/December 2011
Caffeine is the most widely consumed psychoactive drug worldwide. Indeed the majority of adults consume caffeine on a daily basis, most commonly in the forms of coffee and tea. Coffee, in particular, is the favored caffeine source in the United States, where more than 150 million people drink coffee on a daily basis. Coffee, one of the richest sources of antioxidants in the average American's diet, contains caffeine and other antioxidants that have the potential to confer both beneficial and adverse health effects. A growing body of research shows that coffee drinkers, compared to nondrinkers, may be less likely to develop type 2 diabetes, stroke, death from any cause, and neurodegenerative diseases including Parkinson's and Alzheimer's. Coffee appears to have a neutral effect on cardiovascular health. Although more research is clearly needed, coffee, when consumed without added cream or sugar, is a calorie-free beverage that may confer health benefits, especially when used in individuals who do not have adverse subjective effects due to its stimulating effects, and when coffee is substituted for less healthy, unnatural, and/or high-calorie beverages, such as colas and other sugary and artificially sweetened sodas and soft drinks.
Coffee is one of the most widely consumed pharmacologically active beverages across the world. Because of the remarkably wide prevalence of daily coffee consumption, even small health effects could have a large impact on public health. Accumulating evidence from recent epidemiological studies suggest that consumption of coffee has been associated with prevention or delay of degenerative diseases including type 2 diabetes mellitus (T2DM), cardiovascular (CV) disease, Parkinson's disease (PD), Alzheimer's Disease (AD)1-3, death from any cause, and some cancers.4 These potential benefits have been attributed in part to the antioxidants present in coffee 5, moderate weight reduction6,7, increased insulin sensitivity and reduced inflammation8,9 associated with regular coffee consumption. Coffee and tea have been recommended by a United States (US) expert panel consensus statement to be consumed in greater quantities, especially as substitutes for caloric beverages, such as sweetened (with various sugars or artificial sweeteners) nutrient-poor beverages, sports drinks, alcoholic beverages, and even full-fat milk and fruit juices (which are both high in calories).10 However, the specific effects of chronic coffee intake on health, specifically of the heart, blood vessels and brain, remain uncertain? This issue is relevant and important since the majority of adult Americans drink coffee on daily basis. The aim of this review is to discuss the effects of coffee on the CV system and all-cause mortality based on available review of the literature.
Over 50% of Americans above age 18 drink coffee on a daily basis, and another 30% of the population drinks coffee occasionally; making coffee an important environmental exposure affecting 150 million individuals in the US alone. The average consumption in the US is 3.2 cups of coffee per day; men drink as much coffee as women. The average coffee cup size is 9 oz; 65% of all coffee is consumed during breakfast hours, 30% between meals, and the remaining 5% with other meals. Coffee is one of the world's most highly valued and traded commodities, accounting for over $70 billion annually in retail sales. The US, where 400 million cups of coffee are consumed every day, is the leading consumer of coffee in the world.11
Coffee contains over a thousand different biochemical molecules, many formed during the roasting process. Essential compounds found in coffee include: caffeine, diterpene alcohols, chlorogenic acid and other polyphenols. Caffeine is a major component of coffee and its content is highly variable. Coffee provides 71% of the caffeine in the US diet.12 An 8-oz cup of home-prepared brewed coffee (150 ml) contains between 120 and 180 mg of caffeine.13 Specialty coffees consumed in popular US coffee houses typically contain about 160 mg of caffeine per 8 oz but often are served in 12 to 20 oz single-serving containers which will contain approximately 240 to 415 mg of caffeine, respectively. Brewed decaffeinated coffees contain about 5 to 15 mg of caffeine per 8 oz.14 Caffeine exerts its main effects as a potent antagonist of adenosine receptors in the central and peripheral nervous systems, thereby stimulating excitatory neurotransmitters.15 Notable physiological effects associated with caffeine are: central nervous system stimulation, increased metabolic rate, and diuresis; and in a caffeine-naïve person, acute elevation of blood pressure (BP).16
The diterpenoid alcohols are the oils present in coffee that may raise cholesterol; their concentration varies depending on how the coffee is prepared. Filtered coffee has less than 0.1 mg/100 ml, and unﬁltered coffee can have between 0.2 and 18 mg/100 ml.12 Boiled coffee has a higher concentration of coffee oils because of the higher temperature used during its preparation, and a longer contact time between the coffee grounds and hot water.17,18 Diterpenoids in unfiltered coffee may raise plasma low-density (LDL) cholesterol and lower high-density (HDL) cholesterol19, but there is also a potentially positive aspect to these coffee oils in that they have been shown to possess anti-carcinogenic properties.20
Coffee is a rich source of polyphenols such as caffeic acid and chlorogenic acid, as well as caffeine; and coffee has been shown to improve adipocyte and liver function. In a randomized controlled trial of 45 middle-aged, non-diabetic, overweight adults, 5 cups daily of caffeinated coffee raised levels of adiponectin (a hormone that reduces risk for type 2 diabetes and atherosclerosis) and lowered fetuin-A levels, suggesting improved hepatic function.21 These polyphenols also inhibit deoxyribonucleic acid (DNA) methylation in a dose-dependent manner, which prevents down regulation of tumor suppressor proteins and DNA repair enzymes involved in carcinogenesis.22 A 200 ml (7 oz) cup of coffee has been reported to contain 70-350 mg of chlorogenic acid and about 35-175 mg of caffeic acid.23 Coffee also contains several other antioxidants of varying potency may confer beneficial effects.24-26
Unidentified compounds in coffee, other than caffeine, temporarily activate the sympathetic system and may increase blood pressure (BP).27 This effect occurs primarily in non-habitual coffee drinkers, and quickly dissipates with regular coffee consumption. Several micronutrients found in coffee, including magnesium, potassium, niacin, and vitamin E, may contribute to the potential health benefits associated with chronic coffee consumption.
Over the past three decades, many epidemiologic studies have extensively examined the CV effects of coffee consumption, yet the issue remains controversial. Case-control studies have tended to implicate coffee as potentially increasing CV risk, whereas prospective cohort studies have tended to show no associations with coffee intake and CV disease, even among individuals with higher coffee consumption.28,29 A brief review of relevant findings follows.
Many studies have evaluated coffee consumption in relation to risk of coronary heart disease (CHD). The Coronary Artery Risk Development in Young Adults (CARDIA) 30 was a cohort of 5,115 white and black adults who were aged 18 to 30 years when they completed a baseline clinic examination from 1985 to 1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between coronary artery calcification (CAC) or high carotid intima-media thickness and the average consumption (at years 0 and 7) of coffee, decaffeinated coffee, or caffeine. The authors of that study concluded that there is no substantial association between coffee or caffeine intake and coronary and/or carotid atherosclerosis.
A prospective cohort study4 of 3,497 diabetic men without CHD (nonfatal myocardial infarction/MI or fatal CHD) and stroke at baseline, evaluated the risk of CV disease after regular consumption of 4 cups of coffee. After adjustment for age, smoking, and other CV risk factors, relative risks (RRs) were 0.88 (95% CI 0.50-1.57) for CHD (P for trend = 0.29) and 0.80 (0.41-1.54) for all-cause mortality (p for trend = 0.45) for the consumption of ≥ 4 cups/d of caffeinated coffee compared with referent values of 1.0 for non-coffee drinkers. Stratification by smoking and duration of diabetes yielded similar results. These data indicated that regular coffee consumption was not associated with increased risk for CHD or mortality in diabetic men.
A meta-analysis of 21 independent prospective cohort studies31 from January 1966 to January 2008 evaluated of the association of CHD with coffee consumption. This analysis did not support the hypothesis that coffee consumption increases the long-term risk of CHD. In this study, 15,599 CHD cases from 407,806 participants were included. As compared to the light coffee consumption (< 1 cup/d in US or ≤ 2 cups/d in Europe), moderate coffee consumption showed significantly lower CHD (RR 0.82; 0.73-0.92; p < 0.001) in women during the follow-up more than 12 years, and of 0.87 (0.80-0.86) (p = 0.001) in men and women followed 10 years or less. Under the random-effects model, the pooled CHD RR for all studies combined were 0.96 (0.87-1.06), 1.04 (0.92-1.17) and 1.07 (0.87-1.32) for the moderate (1-3 or 3-4 cups/d), heavy (4-5 or 5-6 cups/d) and very heavy (≥ 6 or ≥ 7 cups/d) categories of coffee consumption (all p > 0.05), respectively.
A recent analysis of a large cohort of women with established CV disease from the Nurses' Heart Study found that coffee intake had no effect on either total mortality or CV mortality.32 There was also no association between caffeine intake and either total or cardiovascular mortality. The authors concluded that coffee drinkers who develop heart disease need not discontinue their coffee consumption, as it seems to have no effect on subsequent risk of suffering a fatal event.
Heart rate variability (HRV) is an independent predictor of prognosis in patients who have survived ST-segment elevation myocardial infarct (MI) (STEMI).33,34 Reduction in HRV occurs immediately following an acute MI, can remain suppressed for days to months, and when present predicts a poor CV prognosis.35 A randomized controlled trial36 involving 103 patients with acute STEMI evaluated the effect of acute ingestion of coffee on autonomic function and CV health. These patients randomized to receive regular (caffeinated) or de-caffeinated coffee. In the group randomized to regular coffee, parasympathetic activity increased by up to 96% (p = 0.04) after 5 days. There was no detrimental effect of regular coffee on cardiac dysrhythmias post -STEMI. The authors concluded that coffee ingestion was associated with an increase in parasympathetic autonomic function immediately post-STEMI and was found to be safe and not associated with adverse CV outcomes during the 12 months of follow up. Additionally, a recent study found that coffee improves endothelial function in patients with CHD as well as in those without CHD.37
A recent prospective, observational study38 of 34,551 participants of the Swedish Mammography Cohort aged 48-83 years females evaluated the relationship between coffee consumption and risk of developing heart failure (HF). Patients included in this study did not have HF, diabetes, or MI at baseline. Over 9 years of follow-up, 602 HF events occurred. Women who consumed ≥ 5 cups of coffee per day did not have higher rates of HF than those who consumed < 5 cups per day (multivariable-adjusted hazard ratio = 0.93, 95% confidence interval: 0.72-1.20). Further adjustment for self-reported hypertension (HTN) did not change the results. The authors concluded that there was no association between coffee consumption and incidence of HF in middle-aged and older women.
HTN is a recognized risk factor for CHD and stroke. It has been well established that acute consumption of caffeine at dietary levels raises BP in caffeine-naïve normotensive and particularly in hypertensive individuals by as much as 10 mm Hg.27,39-41 A 200-250-mg dose of caffeine, equivalent to the amount in 1.5 to 2 cups of coffee, has been found to increase systolic BP by 3-14 mmHg and to increase diastolic BP by 4-13 mmHg in normotensive caffeine-naïve individuals.42Caffeine can also potentiate (by about 5 to 10 mmHg) the rise in BP induced by stress, such as that occurring in the workplace, but this effect is largely limited to non-habitual (caffeine naïve) coffee drinkers.43,44 It appears that acute effects of caffeine are transient, and that with habitual use (even after just several days of regular consumption) the adverse humoral and hemodynamic effects of caffeine are markedly attenuated.45
The effects of chronic caffeine ingestion, however, are less clear. Coffee intake was not associated with elevated BP or an increased incidence of HTN in several studies.46-49 The Nurses' Health Study demonstrated that daily intake of up to six cups of coffee or black tea was not associated with an increased risk of HTN.49 However, there is some evidence that chronic caffeine use can cause a small elevation in BP in some individuals.50 A meta-analysis of 18 controlled clinical trials found that coffee ingestion increased systolic and diastolic BP by 1.2 and 0.49 mmHg, respectively.51 Consistent with this observation is that small reductions (about 1 mm Hg) in BP may be seen when habitual coffee drinkers either abstain from coffee or switch to decaffeinated coffee.52,53 A recently published systematic review and meta-analyses of 6 long-term prospective studies that examined the association of habitual coffee consumption with risk of HTN concluded that habitual coffee consumption of >3 cups/d, was not associated with an increased risk of HTN compared with <1 cup/day; however, a slightly elevated risk appeared to be associated with light-to-moderate consumption of 1 to 3 cups/day.54
The effect of coffee may not be solely explained by caffeine. In a study of 15 volunteers (6 habitual and 9 non-habitual coffee drinkers), intravenous caffeine increased muscle sympathetic nerve activity and BP to a similar degree in both groups.27 Furthermore, non-habitual drinkers had similar elevations in BP and muscle sympathetic nerve activity with caffeinated and decaffeinated coffee.
a Mid America Heart & Vascular Institute, Saint Luke's Hospital of Kansas City, Kansas City, MO
b John Ochsner Heart and Vascular Institute, Ochsner Clinical School - The University of Queensland School of Medicine, New Orleans, LA
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