Coffee Consumption and Serum Lipids: A Review of Epidemiological Studies and Experimental Studies in Humans
Coffee Consumption and Serum Lipids: A Review of Epidemiological Studies and Experimental Studies in Humans
45
Coffee Consumption and Serum Lipids:
A Review of Epidemiological Studies
and Experimental Studies in Humans
Defu Ma1, Li Cai2, Xiaolong Han3, Peiyu Wang1
1Department of Social Medicine and Health Education, School of Public Health, Peking University Health Science
Center, Beijing, China; 2Department of Nutrition and Food Hygiene, School of Public Health, Peking University Health
Science Center, Beijing, China; 3Department of Space Food and Nutrition, China Astronaut Research and Training
Center, Beijing, China
lipid concentrations was reported in men with CHD.10 7368 men aged 20–54 years, and found that coffee con-
This possible association was subsequently studied in sumption was positively associated with levels of TC
many cross-sectional observational studies. However, and TG in both sexes and was inversely associated with
cross-sectional studies investigating the associations levels of HDL-C in women. After adjustment for all
have yielded conflicting results. Several cross-sectional covariates including age, logarithm of body mass index,
studies reported that coffee consumption is associated physical activity in leisure time, cigarette smoking, and
with elevated levels of total serum cholesterol.11,12 In alcohol consumption, the TC level was 5.56 mmol/l in
the contrary, other studies did not show an association men drinking less than one cup of coffee a day, compar-
between coffee consumption and serum cholesterol lev- ing with 6.23 mmol/l in those consuming more than nine
els.13,14 In total, most of early observational studies did cups a day. The corresponding figures for women were
report a relationship between coffee intake and serum 5.32 and 5.92 mmol/l.19 It is noteworthy that boiled cof-
cholesterol, but many were limited by failure to control fee was the predominant type consumed by the Tromso
for important confounding variables such as smoking sample. In an extensive meta-analysis of cross sectional
and alcohol drinking.15,16 For example, one study by studies, Bak showed a positive relationship between cof-
Klatsky et al. reporting that coffee consumption was fee and serum TC with statistical significant findings for
positively correlated with serum cholesterol levels did boiled coffee, espresso coffee, and Turkish coffee. The
not adjust tea consumption, which raised the question of common feature of these brewing methods is that no
whether caffeine or some other component is related to paper filter is used during preparation of the coffee.20
the observed effects.15 Williams et al. also showed a posi-
tive correlation between coffee consumption and eleva-
tions of serum apolipoprotein B, low-density lipoprotein 45.3 EXPERIMENTAL STUDIES ON
cholesterol (LDL-C), and total cholesterol (TC), but the COFFEE CONSUMPTION AND SERUM
cross-sectional nature of the design limits inferences LIPIDS
about causality.16 On the other hand, other observational
studies have shown no relationship.12,17 For example, The effect of coffee consumption on cholesterol has
Dawber et al. reported that there was no correlation also been studied in randomized controlled trials. The
between reported level of coffee consumption and the first experiment on coffee consumption and blood cho-
serum total cholesterol level.12 lesterol in hypercholesterolemic subjects was described
In 1987, Thelle et al. reviewed 22 cross-sectional by Egede-Nissen in 1970, and the author suggested that
studies involving 130,000 persons from eight different subjects abstaining from coffee could reduce their TC
countries.9 Results of these reports displayed a variety level by 17%.21 However, subsequent trials indicated
of trends in the association between coffee intake and that this effect was only seen with boiled but not filter-
serum cholesterol concentrations: 8 (36%) studies dem- brewed or instant coffee. In the trials conducted by the
onstrated a significant positive association in both sexes, Tromso, a Norway group, they had consistently found
and 5 (23%) studies showed no association in men or a positive correlation between coffee consumption and
women. In three other reports where both sexes were serum cholesterol levels.22 However, these studies did
included, significant positive association was observed not control dietary and smoking factors. Moreover, the
only in women. The remaining six investigations exam- method of preparation of coffee used, predominantly
ined only men with 4 (18%) reporting a significant cor- boiled, was different from the methods in general used
relation between coffee and cholesterol. Thelle et al. in the United States today. In addition, these studies
concluded that different brewing method and differ- permitted tea consumption, although there was dis-
ent population may be important factors in the choles- agreement in the literature as to whether caffeinated tea
terol-raising effect of coffee. Similarly, Rosmarin et al. causes the same results. Other clinical trials using differ-
reviewed 25 cross-sectional studies and found that 13 ent methods for preparing the coffee have failed to show
observational studies have reported a definite associa- an effect of coffee consumption on lipids.
tion between coffee consumption and elevated lipids, six Clinical trials used various intake levels of coffee with
studies have shown an association only in certain sub- varying types of coffee, and different protocols. To pre-
groups, and six have shown no association.18 Subsequent cisely evaluate the effects of coffee intake on serum lipids
cross-sectional studies and experimental studies have and to clarify the active factors of coffee, Jee et al. per-
proved that boiled coffee exerted significant increasing formed a meta-analyses of nine randomized controlled
effects on serum lipids comparing with that of filtered trials (RCTs) published prior to December 1998 and
coffee.19,20 The Tromso Heart Study examined the rela- found that there was a dose–response relation between
tion between coffee consumption and levels of serum coffee consumption and both TC and LDL-C (p < 0.01).23
TC, high-density lipoprotein cholesterol (HDL-C), and Increases in serum lipids were greater in studies of
triglycerides (TG) in a population of 7213 women and patients with hyperlipidemia and in trials of caffeinated
TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TG, triglyceride.
II. EFFECTS OF COFFEE CONSUMPTION
Reprinted from Ref. 26, with permission from the Nature Publishing Group.
413
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FIGURE 45.1 Meta-analysis of the effect of coffee consumption on TC (A), LDL-C (B), HDL-C (C), and TG (D) compared with control.26
WMD, weighted mean difference; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol;
TG, triglyceride. Reprinted from Ref. 26, with permission from the Nature Publishing Group.
45.4 BOILED COFFEE AND FILTER COFFEE 415
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Overall 22 8.1 <0.001 67.3% 15 5.4 (1.4, 9.5) 0.002 58.4% 11 12.6 (3.5, 21.6) 0.001 66.4%
(4.5, 11.6)
Study design
Parallel 15 7.2 0.001 61.1% 11 4.5 (0.6, 8.5) 0.018 53.4% 6 7.3 (−2.5, 17.1) 0.008 68.1%
(3.3, 11.0)
Cross- 7 10.5 <0.001 78.6% 4 11.5 0.009 74.1% 5 24.1 (10.3, 37.8) 0.247 26.1%
over (1.7, 19.2) (−4.6, 27.5)
Decaffeinated
Yes 3 3.5 0.449 0.0% 2 6.3 0.295 8.7% 1 3.5 (−10.6, 17.7) – –
(−1.1, 8.1) (−0.8, 13.4)
No 19 9.2 <0.001 70.7% 13 5.5 0.001 62.8% 10 13.8 (3.7, 24.0) 0.001 68.7%
(5.0, 13.4) (0.8, 10.2)
Filtered
Yes 10 3.6 (0.6, 6.6) 0.524 0.0% 9 2.3 0.349 10.4% 5 3.7 (−4.2, 11.7) 0.432 0.0%
(−1.1, 5.6)
No 12 12.9 <0.001 79.3% 6 11.9 0.002 73.3% 6 18.8 (4.8, 32.7) 0.001 77.1%
(6.8, 18.9) (3.2, 20.6)
Duration
<8 weeks 11 9.2 <0.001 69.6% 5 9.3 0.028 63.2% 6 15.8 (1.8, 29.8) 0.006 69.3%
(3.8, 14.5) (0.9, 17.8)
≥8 weeks 11 7.3 0.001 68.0% 10 4.0 0.009 59.1% 5 9.7 (−3.8, 23.2) 0.009 70.2%
(2.1, 12.6) (−0.8, 8.9)
Amount of coffee
<6 cups 11 4.2 (1.3, 7.1) 0.109 36.3% 10 2.7 0.419 2.2% 5 0.7 (−5.5, 6.9) 0.884 0.0%
(−0.1, 5.4)
≥6 cups 11 15.7 <0.001 75.2% 5 15.3 0.022 65.0% 6 25.3 (17.0, 33.7) 0.367 7.8%
(7.6, 23.9) (4.5, 26.0)
TC (mg/dl) LDL-C (mg/dl) TG (mg/dl)
Age (years)
<40 11 5.6 (2.0, 9.2) 0.025 51.3% 8 5.4 0.030 54.9% 6 11.5 (1.3, 21.6) 0.033 58.7%
(−0.0, 10.8)
≥40 11 12.4 <0.001 76.0% 7 5.9 0.007 66.4% 5 15.8 (−3.4, 35.0) 0.001 77.3%
(5.1, 19.8) (−0.8, 12.7)
Sex
Male 11 4.5 (0.2, 8.8) 0.033 49.1% 8 3.0 (0.2, 5.7) 0.445 0.0% 5 0.7 (−5.5, 6.9) 0.884 0.0%
Male and 11 11.4 <0.001 75.8% 7 10.7 0.003 69.3% 6 25.3 (17.0, 33.7) 0.367 7.8%
female (5.7, 17.2) (0.8, 20.7)
II. EFFECTS OF COFFEE CONSUMPTION
Hyperlipidemic
No 17 5.6 (2.7, 8.5) 0.006 52.8% 13 4.2 (0.6, 7.7) 0.034 46.4% 9 11.1 (1.7, 20.4) 0.001 69.7%
Reprinted from Ref. 26, with permission from the Nature Publishing Group.
417
418 45. COFFEE CONSUMPTION AND SERUM LIPIDS
beans, which contains cafestol but negligible kahweol, men, regardless of source of caffeine in a cross-sectional
also raised serum cholesterol.35 These findings showed study.41 In another cross-sectional study, after adjusting
that serum cholesterol is raised by cafestol and pos- for age and adiposity, the mean serum cholesterol level
sibly also kahweol, both natural components of coffee was 11 mg/dl higher for women consuming 200 mg or
beans. In addition, Weusten-Van et al. found that cafestol more of caffeine per day compared with those consum-
increased serum TG and alanine amino-transferase and ing less.42 Nevertheless, one study found that serum
depressed serum creatinine and γ-glutamyl-transferase. caffeine concentrations were closely positively related
After withdrawal, γ-glutamyl-transferase activity rose to TG in caffeine-drug users, but no associations were
above baseline.35 Therefore, they concluded that cafes- found between serum caffeine concentrations with TC
tol increased the cholesterol level by alterations in liver or LDL-C levels either in caffeine/drug users or nonus-
function enzymes. In addition, some researchers have ers.43 In addition, Du et al. concluded that chronic intake
reported that cafestol and kahweol increased the syn- of caffeine (exclusively from diet source) might slightly
thesis of cholesterol by decreasing excretion of bile acids increase HDL-C concentrations in women.43
and neutral sterols.36 Superko et al. found an increase of LDL-C and apoli-
poprotein B in subjects consuming decaffeinated filtered
coffee, without any increase among drinkers of normal
45.5 CAFFEINATED COFFEE AND coffee, which suggested that a coffee component other
DECAFFEINATED COFFEE than caffeine was responsible for the LDL-C, apolipopro-
tein B, and lipase activity changes.28 Nevertheless, Fried
As far as the composition of coffee is concerned, caf- et al. reported a significant positive association between
feine is no doubt considered as its major and active consumption of filtered normal coffee and serum lipids.
ingredient. Caffeine is white crystalline powder having a They observed an increase of TC in the group consum-
bitter taste. It was first isolated from coffee in 1820. Often, ing 720 ml per day of filtered normal coffee, while no
coffee is consumed for its stimulatory effects owing to its increase was observed in the group drinking 720 ml of
rich phytochemistry among which caffeine is the most filtered decaffeinated coffee, and in the group drinking
prominent. Coffee is the richest source of caffeine and 320 ml of filtered normal coffee.27 In our subgroup meta-
240 ml instant coffee contains approximately 100 mg of analysis, caffeinated coffee had significant effects on TC,
caffeine. Frary et al. conducted a survey regarding caf- LDL-C, and TG but decaffeinated coffee had not (Table
feine intake from different sources and reported that 45.2). However, these results should be interpreted cau-
70% of caffeine comes from coffee while soft drinks tiously, as only three RCTs involving decaffeinated cof-
and tea contribute 16% and 12%, respectively.37 Ameri- fee were identified in our meta-analysis and two of them
cans annually consume about 139 billion cups of coffee used filtered coffee.26
(20% decaffeinated) with a total caffeine consumption Regarding the lack of an effect of decaffeinated coffee
equivalent to a per capita intake of 125 mg caffeine/day on lipoprotein cholesterol levels, it may be speculated
from coffee, suggesting that caffeine in coffee is the most that the decaffeination process also extracts the active
commonly ingested drug in the United States.38 Because substance(s) or that the coffee beans used to manufacture
of the large number of people consuming coffee, even decaffeinated coffee lack the active substances. A typical
relatively small effects of caffeine on serum lipids might roasted Arabica coffee is composed of 9% protein, 30.4%
eventually have large public health consequence. carbohydrate, 13% lipids, 0.4% volatile acids, 4.2% non-
In 1965, Bellet et al. reported a clinical trial testing volatile acids, 1.6% alkaloids, 4% ash, 2.5% water, and
the effect of caffeine on the level of fatty acids and did 35% browning compounds, which include phenolic com-
not find positive relationship.39 Since then, a number of pounds.44 Robusta coffee has a much higher phenolic
investigations in humans have been published. In most content than coffee Arabica. In addition, the content of
cross-sectional studies on caffeine and serum lipids, only cafestol and kahweol is also highly dependent on the ratio
caffeine intake from coffee is positively associated with of Arabica/Robusta coffee species, as beans from coffee
serum cholesterol. Curb et al. found a positive relation- Arabica contain more of cafestol and kahweol than those
ship between coffee consumption and serum cholesterol, from coffee Robusta. It has been reported that Robusta
but there was no significant relationship between tea or bean is used to a greater extent in decaffeinated coffees. In
cola, the other major caffeine contributors to the diet, the section of boiled coffee and filter coffee, we have stated
and serum cholesterol. Thus, this analysis concluded that the diterpenes cafestol and kahweol may be respon-
that there was a significant positive relationship between sible for the increase in plasma cholesterol. Therefore, the
caffeine from coffee and serum cholesterol which is not cholesterol-increasing effect difference between boiled
present with other sources of caffeine.40 Mathais et al. coffee and filtered coffee which have the similar content
found a significant dose–response relationship between of caffeine indicated that a coffee component other than
caffeine consumption and TC in women but not in caffeine was responsible for the cholesterol-increasing
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