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KEY WORDS
Coffee, inflammation, C-reactive protein,
CRP, endothelial dysfunction, cross-sectional study, Nurses Health
Study, type 2 diabetes, women
INTRODUCTION
888
Evidence also exists that dietary factors might influence the risk
of cardiovascular disease through modulation of endothelial
function (2 4).
Several studies have found that coffee consumption is associated with an impairment of the flow-mediated dilatation of the
brachial artery (5), aortic stiffness, and wave reflections (6). In
addition, a cross-sectional study found that moderate coffee consumption is related to an increase in plasma concentrations of
several markers of general inflammation (7). On the other hand,
prospective studies have reported that coffee consumption is not
associated with an increased risk of coronary heart disease (8
10), and epidemiologic studies have consistently linked coffee
consumption with a lower risk of type 2 diabetes mellitus (11). In
the present study, we evaluated the associations between longterm consumption of caffeinated and decaffeinated filtered coffee and plasma markers of inflammation and endothelial dysfunction in healthy and diabetic women in the Nurses Health
Study (NHS).
SUBJECTS AND METHODS
Subjects
The NHS was established in 1976 and included 121 700 female registered nurses residing in the United States. Every 2 y,
participants are mailed a follow-up questionnaire to update information about their medical history, lifestyle, and other risk
factors. The present study included 2 subcohorts. One subcohort
consisted of 730 women selected as control subjects for an earlier
nested case-control study of type 2 diabetes (12) and who had not
been diagnosed with cardiovascular disease, cancer, or type 2
diabetes mellitus at the time of the blood collection in 1989
1990. The second subcohort included 663 women who provided
blood samples and had a confirmed diagnosis of type 2 diabetes
mellitus but not of cardiovascular disease or cancer (13). We also
excluded those women who reported insulin use, because this
1
From the Departments of Nutrition (EL-G, RMvD, LQ, and FBH) and
Epidemiology (FBH), Harvard School of Public Health and the Channing
Laboratory (FBH), Harvard Medical School, Boston, MA.
2
Supported by NIH research grants HL65582 and DK58845. FBH was
partially supported by an American Heart Association Established Investigator Award.
3
Reprints not available Address correspondence to E Lopez-Garcia, Department of Preventive Medicine, Universidad Autonoma de Madrid, Arzobispo Morcillo, 2 Madrid, Spain. E-mail: esther.lopez@uam.es.
Received February 9, 2006.
Accepted for publication May 18, 2006.
Am J Clin Nutr 2006;84:888 93. Printed in USA. 2006 American Society for Nutrition
ABSTRACT
Background: In several short-term studies, coffee consumption has
been associated with impairment of endothelial function.
Objective: The objective was to assess the relation between longterm caffeinated and decaffeinated filtered coffee consumption and
markers of inflammation and endothelial dysfunction.
Design: We conducted a cross-sectional study of 730 healthy
women and 663 women with type 2 diabetes from the Nurses Health
Study I cohort, who were aged 4370 y and free of cardiovascular
disease and cancer at the time blood was drawn (1989 1990). Dietary intake was assessed with a validated food-frequency questionnaire in 1986 and 1990.
Results: About 77% of the healthy women consumed 1 cup (237
mL) caffeinated coffee/mo and 75% consumed 1 cup decaffeinated coffee/mo; the corresponding intakes for women with type 2
diabetes were 74% and 63%, respectively. In healthy women, no
appreciable differences in plasma concentrations of the markers
were found across categories of caffeinated coffee intake. In women
with type 2 diabetes, higher caffeinated coffee consumption was
associated with lower plasma concentrations of E-selectin (adjusted
percentage change per 1 cup/d increment 3.2%; P 0.05) and
C-reactive protein (adjusted percentage change 10.2%; P
0.001). Higher decaffeinated coffee consumption was associated
with lower plasma concentrations of E-selectin (adjusted percentage
change 2.5%; P 0.08) and C-reactive protein (adjusted percentage change 7.9%; P 0.02) only in healthy women. The
results were similar when we also adjusted the models for other
dietary factors and blood lipids and when we excluded participants
with hypertension or hypercholesterolemia.
Conclusions: These results indicate that neither caffeinated nor
decaffeinated filtered coffee has a detrimental effect on endothelial
function. In contrast, the results suggest that coffee consumption is
inversely associated with markers of inflammation and endothelial
dysfunction.
Am J Clin Nutr 2006;84:888 93.
RESULTS
889
890
LOPEZ-GARCIA ET AL
TABLE 1
Characteristics of the population in 1990 by categories of total coffee consumption (average between consumption in 1986 and 1990)1
Healthy women
1 cup/mo
(n 60)
1 cup/mo to
4 cups/wk
(n 80)
57 cups/
wk
(n 211)
2 cups/d
(n 379)
P for
trend
1 cup/mo
(n 71)
1 cup/mo to
4 cups/wk
(n 106)
57 cups/
wk
(n 331)
2 cups/d
(n 155)
P for
trend
56 0.92
12
26.7 0.8
14.9 2.2
8
17
23
37
4.7 1.1
84 12
285 9
2.6 0.1
0.63 0.02
5.0 0.3
105 1.9
1.2 0.2
4.6 0.4
2.1 0.2
0.11 0.02
0.31 0.04
5.6 0.4
55 0.8
4
26.1 0.6
16.8 2.3
19
28
30
40
4.3 0.9
85 9
299 9
2.4 0.1
0.68 0.01
5.0 0.3
106 2.3
1.2 0.2
2.7 0.2
1.9 0.2
0.13 0.02
0.36 0.04
6.2 0.3
57 0.5
9
26.8 0.5
14.4 1.3
25
34
27
42
4.4 0.5
171 7
298 5
2.6 0.06
0.67 0.7
4.9 0.2
104 1.1
0.6 0.05
3.4 0.1
2.0 0.1
0.13 0.01
0.34 0.02
6.2 0.2
56 0.4
16
26.1 0.3
16.3 1.8
17
30
30
46
6.8 0.6
356 10
315 3
2.5 0.04
0.70 0.01
5.0 0.1
99 0.9
0.5 0.04
3.4 0.1
2.2 0.1
0.11 0.01
0.35 0.02
5.9 0.1
0.18
0.98
0.70
0.57
0.005
0.01
0.01
0.45
0.84
0.001
0.34
0.57
0.26
0.70
0.58
0.001
0.08
0.91
0.49
0.82
0.21
57 0.8
8
32.5 0.8
13.8 2.3
45
37
20
44
1.5 0.7
83 11
284 8
1.5 0.1
0.68 0.01
5.1 0.4
107 2.3
0.9 0.1
1.3 0.2
2.0 0.2
0.23 0.06
0.31 0.08
5.2 0.6
59 0.7
3
30.8 0.5
13.8 1.6
47
41
33
41
2.8 1.2
98 12
302 8
1.5 0.06
0.67 0.02
5.2 0.3
106 1.9
0.8 0.1
0.7 0.1
2.6 0.3
0.10 0.02
0.31 0.05
4.8 0.3
59 0.4
12
30.4 0.3
12.6 0.8
45
43
22
48
2.9 0.4
211 8
309 4
1.5 0.03
0.68 0.01
5.0 0.2
103 1.0
0.5 0.04
0.9 0.1
2.9 0.2
0.11 0.01
0.33 0.03
5.2 0.2
59 0.5
24
29.5 0.5
12.2 1.2
45
37
21
45
3.7 0.6
377 22
322 6
1.6 0.05
0.67 0.01
4.9 0.2
100 1.3
0.6 0.07
0.7 0.08
3.5 0.4
0.21 0.05
0.60 0.09
7.0 0.7
0.09
0.001
0.005
0.37
0.87
0.67
0.74
0.67
0.12
0.001
0.001
0.10
0.75
0.39
0.002
0.01
0.02
0.006
0.10
0.001
0.001
drink more alcohol than those in the lower ones. When comparing the extreme categories, caffeine intake varied from 84 to 356
g/d among healthy women, and from 83 to 377 g/d among diabetic women; also, magnesium intake increased from 285 to 315
mg/d and from 284 to 322 mg/d, respectively. In addition, coffee
consumption was associated with lower glycemic load and lower
tea consumption.
We calculated mean plasma concentration markers by categories of coffee consumption and observed higher values for all
markers in women with type 2 diabetes (Tables 2 and 3). In
healthy women, no appreciable differences across categories of
caffeinated coffee were found, except a marginally inverse association between increasing coffee intake and decreasing
plasma concentrations of sTNF-R2 (adjusted percentage change
per 1 cup/d increment 2.1%; P 0.08 from the linear
regression model) (Table 2). In women with type 2 diabetes, we
found an inverse association of caffeinated coffee with plasma
E-selectin concentrations (adjusted percentage change 3.2;
P 0.05) and a stronger inverse association with CRP (adjusted
percentage change 10.2; P 0.001). These results were
similar when we used caffeine intake instead of caffeinated coffee consumption. For decaffeinated coffee (Table 3), we observed a marginally inverse association between coffee consumption and the concentration of E-selectin (adjusted
percentage change 2.5; P 0.08) and CRP (adjusted percentage change 7.9; P 0.02) in the subcohort of healthy
women. Finally, no association between decaffeinated coffee
and the studied markers was seen in diabetic women.
In additional analyses, we observed similar results when we
further adjusted the models for the nutrients and foods that could
confound the association. Similarly, adjustment for total cholesterol and plasma triacylglycerols did not modify the results, nor
Age (y)
Current smoker (%)
BMI (kg/m2)
Physical activity (MET-h/wk)
Hypertension (%)
Hypercholesterolemia (%)
Postmenopausal hormone use (%)
Aspirin use (%)
Alcohol consumption (g/d)
Caffeine (mg/d)
Magnesium (mg/d)
trans Fat (% of energy)
Total n3 fatty acids (% of energy)3
Cereal fiber (g/d)
Glycemic load
Tea (cups/d)4
Soft drinks (servings/d)
Dairy (servings/d)
Processed meat (servings/d)
Nuts (servings/d)
Fruit and vegetables (servings/d)
891
TABLE 2
Adjusted geometric mean (and 95% CIs) plasma concentrations of inflammation and endothelial dysfunction markers by categories of caffeinated coffee
consumption1
Caffeinated coffee consumption
1 cup/mo
57 cups/wk
2 cups/d
Percentage
differences per 1
cup/d increment
P2
167
174
121
140
189
251
253
98
0.40
0.22
0.33
0.49
0.28
0.85
0.11
0.05
0.45
0.33
0.09
0.08
0.14
0.14
0.001
0.001
sICAM-1, soluble intercellular adhesion molecule 1; CRP, C-reactive protein; sTNF-R2, soluble tumor necrosis factor receptor 2.
From multiple linear regression models for the relation between caffeinated coffee consumption (cups/d) and log-transformed markers.
3
Adjusted for age (5-y categories), BMI (in kg/m2: 23.0, 23.0 24.9, 25.0 29.9, 30.0 34.9, and 35.0), quintiles of physical activity (metabolic
equivalent hours/wk), smoking status [never smoker, past smoker, and current smoker (114 and 15 cigarettes/d)], alcohol consumption (nondrinker and
0 4.9, 5.0 9.9, 10 14.9, and 15.0 g/d), aspirin use, postmenopausal hormone therapy (premenopausal and never, past, and current user), and categories of
caffeinated soft drinks, tea, and decaffeinated coffee consumption.
1
2
plasma concentrations of interleukin 6, CRP, and TNF-. Because unfiltered coffee was included when coffee consumption
was measured, it is plausible that compounds in this beverage that
increase cholesterol concentrations also contribute to increased
inflammation and endothelial dysfunction (30). Another possible explanation for the differences between our study and theirs
is that we used data on coffee consumption from 2 different
FFQs, which reflect 4 y of consumptiona longer duration than
was used in the ATTICA study.
Our findings are somewhat consistent with the fact that coffee
consumption may reduce inflammation and markers of endothelial activation. Yukawa et al (31) conducted an in vivo study with
11 healthy males who drank 24 g coffee/d for 1 wk and found that
regular coffee ingestion reduced LDL oxidation susceptibility.
Coffee may favorably affect endothelial atherosclerotic plaques
through this pathway, because oxidized LDL is present in atherosclerotic lesions enhancing the process (32). Additionally, the
phenolic compounds of coffee (chlorogenic acid, ferulic acid,
1 cup/mo to 4
cups/wk
892
LOPEZ-GARCIA ET AL
TABLE 3
Adjusted geometric mean (and 95% CIs) plasma concentrations of inflammation and endothelial dysfunction markers by categories of decaffeinated coffee
consumption1
Decaffeinated coffee consumption
1 cup/mo
57 cups/wk
2 cups/d
Percentage
differences per 1
cup/d increment
P2
256
252
200
214
162
149
112
48
0.26
0.47
0.83
0.61
0.06
0.08
0.32
0.44
0.06
0.02
0.37
0.18
0.89
0.76
0.30
0.16
sICAM-1, soluble intercellular adhesion molecule 1; CRP, C-reactive protein; sTNF-R2, soluble tumor necrosis factor receptor 2.
From multiple linear regression models for the relation between decaffeinated coffee consumption (cups/d) and log-transformed markers.
3
Adjusted for age (5-y categories), BMI (in kg/m2: 23.0, 23.0 24.9, 25.0 29.9, 30.0 34.9, and 35.0), quintiles of physical activity (metabolic
equivalent hours/wk), smoking status [never smoker, past smoker, and current smoker (114 and 15 cigarettes/d)], alcohol consumption (nondrinker and
0 4.9, 5.0 9.9, 10 14.9, and 15.0 g/d), aspirin use, postmenopausal hormone therapy (premenopausal and never, past, and current user), and categories of
caffeinated soft drinks, tea, and caffeinated coffee consumption.
1
2
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