Review
Coffee and cardiovascular disease: In vitro, cellular, animal, and human studies

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Abstract

Coffee is a commonly consumed beverage with potential health benefits. This review will focus on cardiovascular disease. There are three preparations of coffee that are commonly consumed and thus worthy of examination; boiled unfiltered coffee, filtered coffee, and decaffeinated coffee. Coffee has over a thousand chemicals, many formed during the roasting process. From a physiological point of view, the potential bioactives are caffeine, the diterpenes cafestol and kahweol found in the oil, and the polyphenols, most notably chlorogenic acid. We will examine coffee and its bioactives and their connection with and effect on the risk factors which are associated with heart disease such as lipids, blood pressure, inflammation, endothelial function, metabolic syndrome and potentially protective in vivo antioxidant activity. These will be critically examined by means of in vitro studies, cell experiments, animal supplementation, epidemiology, and the most definitive evidence, human trials.

Introduction

Coffee is among the most widely consumed pharmacologically active beverages in the world. Caffeine is the most widely consumed psychoactive substance. Since drinking coffee is very common in Western society, it is important that it be investigated. For example 52% of all persons in the US over 10 years of age consume coffee [1]. The latest consumption data for coffee importing countries from the International Coffee Organization are from 2004 and found in Fig. 1 [2]. Finland consumes the most coffee and the United Kingdom the least. The average for the European Community is 5.1 kg/year and is similar to the US. Coffee has recently been recommended by a US review panel to be consumed along with tea in greater quantities than all other beverages save water. These include caloric beverages such as milk, non-calorically sweetened beverages, fruit and vegetable juices, alcohol, sports drinks and calorically sweetened, nutrient-poor beverages [3]. But is coffee good or bad for the heart? That is the question that needs to be answered since heart disease is the number one cause of death in the developed world.

There are two species of coffee trees of commercial importance, Coffea arabica and Coffea robusta. The two species differ in chemical composition of the green coffee bean. Arabica contains more lipids and robusta contains more caffeine and sucrose as well as the polyphenols antioxidant chlorogenic acid and its derivatives [4]. Due to the fact that arabica has a more desirable flavor, this variety constitutes 80% of the world trade. Robusta is often used in instant coffee and as fillers in roast and ground blends [4]. The roasting process causes a loss of water from the green bean and degradation of many of the compounds including the antioxidant polyphenols; however, there is very little difference in total antioxidants between the different roasts of a bean [5]. There are three main methods of coffee preparation; boiled unfiltered coffee, filtered coffee, and decaffeinated coffee, the latter primarily consumed as instant coffee.

Before examination of the evidence, it is wise to appreciate what are probably the bioactives in coffee. There are over a thousand compounds, many formed during the roasting process, which produce the unique taste and smell of coffee [4]. However, from the point of view of concentration in coffee, prior detection of the parent compound or metabolites in the body, and physiological effects, there are essentially only three ingredients that are important; caffeine, the diterpene alcohols cafestol and kahweol, and chlorogenic acid and other polyphenols. Their structures are displayed in Fig. 2. Although caffeine is a major component of coffee, the caffeine content is highly variable. A cup of home prepared coffee (150 ml) contains between 30 and 175 mg [6]. In specialty coffees consumed outside the home the range is 18–80 mg/cup and decaffeinated coffees averaged 5 mg/cup [7]. Coffee is an important source of caffeine; it provides 71% of the caffeine in the US diet [8]. The diterpenoid alcohols are the oils in coffee and their concentration depends on the how the coffee is prepared. Filtered coffee has less than 0.1 mg/100 ml, i.e. essentially none, and unfiltered coffee can have between 0.2 and 18 mg/100 ml depending on the method. The order of decreasing amounts is the following; Scandinavian boiled > Turkish/Greek  French press > Espresso  Filter [9]. 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 water [10], [11].

We hypothesize that the bioactive ingredients in coffee relating to heart disease are the polyphenols which in the body may be acting as protective antioxidants but also could have other beneficial mechanisms. However, the most well-known ingredient in coffee is the alkaloid caffeine. This compound has a variety of pharmacological effects with respect to mood, cognitive performance, and motor activity. At present there is no evidence that caffeine can have any benefit for the heart; on the contrary some results indicate that it is detrimental in certain conditions. Thus, there is a Jekyll and Hyde or yin and yang aspect to coffee. We will attempt to separate the effects of caffeine from the rest of the compounds in coffee as much as possible.

This work will examine coffee and its ingredients, in particular the polyphenols, diterpenes, and caffeine, for potential protective cardiovascular effects on risk factors of heart disease by means of in vitro experiments, cell and animal studies, epidemiology, and lastly human trials.

Section snippets

Diterpenes

The two diterpene compounds cafestol and kahweol are suspected to be the coffee substances which cause the elevation of serum cholesterol. One mechanism may be the LDL receptor which is involved in the endocytic process of apoB- and apoE-containing lipoproteins. Cholesterol content of the cell is regulated via feedback repression of the gene for the LDL receptor. When the cell is depleted of cholesterol, the LDL receptor gene is actively transcribed and LDL is removed from the plasma to

Caffeine

Cellular studies can be a simple way to determine the metabolism of coffee compounds and to discover possible mechanisms for bioactivity in vivo. Caffeine metabolites are inhibitors of the enzyme poly(ADP-ribose)polymerase-1 in hydrogen peroxide-treated epithelial cells at physiological concentrations [32]. This is a potential in vivo anti-inflammatory caffeine function in humans and possibly beneficial to the heart.

Polyphenols

CGA is categorized as a phenolic acid, specifically a hydroxycinnamic acid (see

Caffeine

Animal studies can provide valuable information on the mechanism of cardiovascular benefit with the proviso that doses of bioactives and coffee close to that consumed by humans are used. However, no animal study can with certainty predict the effect on humans. Chronic caffeine supplementation to pregnant monkeys produced no change in cholesterol or triglycerides which were depressed during pregnancy [44]. In a recent article, ovariectomized female rats were investigated as a model of

Human epidemiology studies

Epidemiological evidence can never prove cause and effect for any regimen such as coffee drinking since it cannot account for all the variables. For instance coffee drinkers may have a significantly less healthy lifestyle than tea drinkers. In a European study of men women aged 25–64 years, associations of lifestyle factors with coffee and tea consumption were analyzed [53]. Coffee drinkers smoked more, ate more meat and less fruits than tea drinkers and were more sedentary. The authors

Polyphenol absorption and antioxidant activity

A Dutch study examined the human absorption of CGA and caffeic acid using ileostomy subjects who lack a colon [81]. Study of this group eliminates bacterial degradation of the polyphenols which is extensive in normal humans. By urine analysis they found that CGA and caffeic acid were absorbed 33 and 95% in the body, respectively. Another research team found that the major metabolites from coffee consumption in normal human subjects, after hydrolysis of the conjugated metabolites, were CGA and

Conclusions

Although there have been numerous in vitro studies, cell studies, animal studies and epidemiology investigations with coffee and its bioactive components, there has been a paucity of human trials as shown in this review. This is probably due to the early evidence that boiled coffee increased lipids in humans. The initial negative finding was an obstacle to a scientific assessment of the potential benefits of coffee. From the data presented here, it is concluded that only heavy consumption (>6

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