Coffee consumption has been inconsistently associated with reductions in stroke incidence and stroke mortality in many studies. Habitual coffee consumption could potentially reduce the risk of stroke by increasing insulin sensitivity55,56 and reducing inflammation.8,9 In a study of Finnish patients with T2DM, those who consumed 3 or more cups of coffee per day had a statistically non-significant lower risk of death from stroke compared with those who consumed 2 or fewer cups of coffee per day (RR, 0.73; 95% CI, 0.92 to 1.05).57 Coffee drinking was not associated with risk of total stroke in a cohort of US Health Professionals.58
The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study59, a prospective cohort study of 26,556 Finnish smoker males aged 50 to 69 years without a history of stroke at baseline, concluded that high consumption of coffee (8 cups/day) may reduce the risk of cerebral infarction among men, independent of known CV risk factors.
A recent prospective epidemiological study60 of Swedish Mammography Cohort investigated the association between coffee consumption and stroke incidence in 34,670 women without a history of CV disease or cancer at baseline who were prospectively followed for mean of 10.4 years. After adjustment for other risk factors, coffee consumption was associated with a statistically significant lower risk of total stroke, cerebral infarction, and subarachnoid hemorrhage but not intracerebral hemorrhage. The association between coffee consumption and cerebral infarction was not modified by smoking status, body mass index, history of diabetes or HTN, or alcohol consumption. An analysis of a prospective group of over 83,000 women from the Nurses' Health Study who were free of CV disease and cancer at baseline found that coffee consumption was associated with a modest but statistically significant reduction in the risk of stroke during the 24-year follow up period.61 (Figure 1)
In contrast, the Honolulu Heart Program with 25 years of follow-up of non-smoking and hypertensive men concluded that the risk of thromboembolic stroke was higher for men who consumed 3 cups of coffee per day compared to those who consumed no coffee (RR, 2.1; 95% CI, 1.2 to 3.7).62
Figure 1: Coffee consumption was associated with a significantly reduced risk of stroke in women (p for trend = 0.003) (c = cups of coffee).61
The current literature suggests that antioxidants in coffee (such as chlorogenic acid) may improve glucose metabolism and insulin sensitivity.56 Short-term studies have shown that acute administration of caffeine can induce insulin resistance and impaired glucose tolerance.63,64 However, several prospective long-term studies have shown that consumption of coffee or tea is associated with improved insulin sensitivity and better control of postprandial glycemia in patients with T2DM.55,65,66A recently publish randomized study found that, consumption of 5 cups of coffee per day increases adiponectin as compared to no coffee consumption.21 Increase in plasma adiponectin concentration leads to decreased insulin resistance.67 Caffeine acutely activates 5' adenosine monophosphate-activated protein kinase and insulin-independent glucose transport in skeletal muscle.68 Long-term caffeine consumption up regulates insulin-like growth factor 1 signaling, that in turn enhances insulin sensitivity as well as insulin secretion in a rat model.69
Currently available data suggests that long-term coffee consumption is associated with a decreased risk of T2DM.70-74 (Figure 2) Systematic review of 9 cohort studies comparing minimal to low coffee consumption (< 2 cups/day) to that of > 6 cups/day for risk of developing T2DM. The study concluded that the risk of developing T2DM was lowest in subjects who drank > 6 cups daily (RR 0.65; 0.54-0.78) and significantly reduced for subjects who consumed four to six cups daily (RR 0.72; 0.62-0.83).75 These associations did not differ by sex, obesity, or region, including the US, Europe, and Asia. A modest inverse association was also seen for decaffeinated coffee.
The Nurses' Health Study, a prospective study of over 88,000 women aged 26 to 46 years, found that the risk of T2DM was lower with daily coffee consumption in a dose-dependent fashion, whereby even for small amounts of coffee on a daily basis reduced risk.72 (Figure 4) Associations were similar for non-caffeinated and caffeinated coffee; tea consumption did not affect risk of T2DM.
Figure 2: Habitual coffee consumption was associated with a dose dependent reduction in risk for development of type 2 diabetes (p for trend < 0.001).72
Electrophysiological studies have demonstrated that caffeine might promote arrhythmogenesis. Caffeine can directly increase the trans-membrane calcium current that is responsible for the oscillatory after-potential (i.e. triggered activity) as noted in vitro and in vivo experimental models, in part via release of calcium from the sarcoplasmic reticulum.76-79
A few studies have evaluated the effect of coffee intake on the QT interval and cardiac repolarization. A study of 18 healthy subjects and 18 patients with frequent ventricular ectopic beats reported no significant change in QT interval in either group after caffeine ingestion.47 Another study of 10 healthy volunteers showed that caffeine consumption (400 mg/day, equivalent of 4 cups of coffee) did not affect the QT interval.80 In addition, experiments with canine ventricular muscle models found no effect of caffeine on cardiac action potentials, which may explain its lack of effect on the QT interval.81
Another study82 examined 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988-1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥ 6 cups/d to those who did not drink any were -1.2 ms (95% CI -4.4 to 2.0) for coffee, and -2.0 ms (-11.2 to 7.3) for tea, respectively. The average difference in QT interval comparing the highest vs. the lowest quartiles of caffeine intake was -1.2 ms (-2.7 to 0.3). The study concluded that QT interval duration was not associated with coffee intake of up to 6 cups/day does.
In the Women's Health Study83, 33,638 women > 45 y of age and free of CV disease and AF at baseline were prospectively followed for incident AF from 1993 to March 2009. In this large cohort of initially healthy women, caffeine consumption was not associated with an increased risk of incident AF.
In the Danish Diet84, Cancer, and Health Study 47,949 participants were prospectively followed to determine relationship between caffeine consumption and incidence of atrial fibrillation of flutter. Caffeine was consumed in form of coffee, tea and cola. During follow-up (average 5.7 yrs), consumption of caffeine was not associated with risk of atrial fibrillation or flutter. Similarly, in a Framingham Heart Study cohort85 consumption of caffeine was not significantly associated with AF risk.
No adverse effects of filtered coffee intake on plasma lipids have been shown by many studies.86,87The prospective cohort study of over 132,000 men and women (41,736 men in the Health Professionals Follow-Up Study and 86,216 women from the Nurses' Health Study) found that there was no association between the intake of filtered caffeinated coffee or filtered decaffeinated coffee and serum concentrations of total cholesterol, LDL-cholesterol, or HDL-cholesterol.86 A meta-analysis of 14 randomized controlled trials found that the consumption of boiled coffee dose-dependently increased serum total and LDL-cholesterol concentrations, while the consumption of ﬁltered coffee resulted in very little change in serum cholesterol.88 The cholesterol-raising factors in unﬁltered coffee have been identiﬁed as cafestol and kahweol, diterpenes that are removed from coffee by paper ﬁlters.89
Very limited data has evaluated the impact of coffee consumption and VHD. Cox regression analysis of 1,354 subjects (aged 65.4 to 96.6 years at study entry and then 10 years follow up) from Framingham Heart Study population90 observed a signiﬁcant negative association between caffeinated coffee consumption (> 1 cup/d) and CHD mortality for subjects with systolic BP < 160 mmHg and diastolic BP < 100 mmHg. This decreased risk appeared to be caused primarily by an inverse prospective relation between caffeinated coffee consumption and the development or progression of VHD. The study concluded that caffeinated coffee consumption was associated with lower risk of CHD mortality and development or progression of VHD in older Framingham subjects without moderate or severe HTN.
Parkinson's disease (PD)
Several studies conducted worldwide have described the relationship between coffee and tea consumption and the risk of developing PD. Most of these studies found evidence of a dose-response relationship between coffee or tea intake and decreased risk for PD.91,92 However, heterogeneity and conﬂicting results between studies preclude a correct estimation of the strength of this association. A recent systematic review and meta-analysis of published cohort, case-control and cross-sectional studies observed an inverse relation between levels of exposure to caffeine and risk of developing PD. 2 (Figure 3) The RR for the association between caffeine intake and PD was 0.75 [95% CI: 0.68-0.82]. The authors concluded that there was an inverse association between caffeine intake and the risk of PD, which could not be explained by bias or uncontrolled confounding.
Figure 3: Dose response relation for the association between coffee intake and the risk of Parkinson's disease. Summary relative risk (RR) estimated by weighted least squares regression.2
Alzheimer's Disease (AD)
The studies to date addressing this issue suggest that coffee intake may be associated with a reduced risk of AD. In the CAIDE study93, (CV Risk Factors, Aging and Dementia) coffee drinking of 3-5 cups per day at midlife was associated with a decreased risk of dementia/AD by about 65% at late-life. After an average follow-up of 21 years, coffee drinkers at midlife had lower risk of dementia and AD later in life compared with those drinking no or only little coffee adjusted for demographic, lifestyle and vascular factors, and depressive symptoms.
Additionally, a recent meta-analysis addressing this topic suggested that coffee and caffeine intake may reduce risk of dementia.1 (Figure 4) The neuro-protective effect of coffee may be mediated by antioxidant capacity and increased insulin sensitivity.
Figure 4: Caffeine intake was associated with significant reductions in Alzheimer's disease, dementia, and mild cognitive impairment in this meta-analysis.1
Available date suggest that there is a significant inverse association between coffee consumption and depression and/or suicide94-98. A recently published prospective study98 of 50,739 women who were followed for 10 years showed that compared to consuming 1 or less cup of caffeinated coffee per week, the multivariate relative risk of depression was 0.85 (95% confidence interval, 0.75-0.95) for those consuming 2 to 3 cups per day and 0.80 (0.64-0.99; P for trend <.001) for those consuming 4 cups per day or more. Decaffeinated coffee was not associated with depression risk. Authors concluded that depression risk decreases with increasing caffeinated coffee consumption.
A prospective study, which included the study population of 41,736 men from Health Professionals Follow-Up Study (followed for 18 years) and the Nurses' Health Study (86,216 women followed for 24 years), assessed the relationship between coffee and all-cause mortality.99 The study showed lower mortality rates during follow up in those who consumed generous amounts of coffee on a daily basis. This study reported that drinking 2 or more cups of coffee per day was associated with a significant reduction in all-cause mortality in women after multivariable adjustment, primarily due to a reduction in CV mortality. Additionally a strong trend towards a reduction in all-cause mortality was noted in men consuming 2 or more cups of coffee daily, although it was not statistically significant. Similar findings were noted with decaffeinated coffee, suggesting an effect from a component other than caffeine.99 (Figure 5)
Figure 5: Relationships between coffee intake and total CV mortality.93
Currently available data from prospective studies suggests that coffee consumption may decrease the risk of T2DM, and neurodegenerative diseases such as AD and PD. Coffee does not appear to increase the risk of CHD. Coffee consumption could plausibly confer reductions in risks for diabetes, stroke, total mortality, neuro-degenerative diseases, and depression. The precise nature of the relation between coffee and BP is not yet clear, although most evidence suggests that chronic coffee intake does not raise BP to a clinically significant degree, and does not increase risk of development if HTN. Available data suggest that coffee intake of up to 6 cups/day does not affect QT interval or risk of serious dysrhythmias.
The currently available evidence on coffee consumption and risk of CV disease is largely reassuring. The majority of studies also showed that there may be a modest inverse relationship between coffee consumption and all-cause mortality. The observational data do not prove a cause-and-effect relationship, and thus increasing coffee as a prevention strategy cannot currently be recommended. Additional prospective studies on coffee consumption and its effect on the CV system and brain are warranted.
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