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J Clin Epldemiol Vol. 48, No. 10, pp. 1189-I 196, 19950?3954356(95)ooo23-2 ElsevierScience td. Printed n Great Britain

THE IMPACT OF CHANGES IN COFFEE CONSUMPTIONON SERUM CHOLESTEROL

MING WEI, CAROLINE A. MACERA,* CARLTON A. HORNUNG andSTEVEN N. BLAIR3Department of Internal Medicine, School of Medicine, University of South Carolina, Columbia,SC 29208, Department of Epidemiology and Biostatistics, School of Public Health, University ofSouth Carolina, Columbia, SC 29208 and Cooper Institute for Aerobics Research, Dallas, TX,

U.S.A.(Received in revised form 23 January 1995)

Abstract-To investigate the possible association between changes in coffee consump-tion and serum cholesterol levels, information was obtained from 2109 healthynonsmokers aged 25-65 years at two clinic visits to a preventive medical center between1987 and 1991 (mean interval between visits: 16.7 months). After adjusting for age andchanges in other potential confounders, about 2mg/dl total cholesterol increase wasassociated with an increase of one cup of regular coffee per day (p

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1190 Ming Wei et al.boiled regular coffee have consistently indicatedincreased serum cholesterol [22-251. However,reports on the association between serumcholesterol and filtered regular coffee, which iscommonly consumed in the U.S. and WesternEurope, are much less consistent [27-301. But itshould be realized, as indicated by Fried et al.,that those studies had many limitations includ-ing rather limited samples, the absence ofwashout periods, the lack of data about compli-ance with protocols and confounding variables[3 11.A recent intervention study overcame someof these limitations and demonstrated thatfiltered coffee led to a statistically significantincrease n serum total cholesterol [31]. Since themagnitude of change in cholesterol level wasmild and only 100 healthy male volunteers wereinvolved in the study, more prospective studieswith larger samples, especially those that in-clude women, are needed.The present study analyzed prospective datafrom a large sample of male and female non-smokers to assess he effect of changes in coffeedrinking habits and coffee dose on lipid profiles.

METHODSSubjects for this study were men and womenbetween 25 and 65 years of age (mean + SD:48.2 &- 8.6 years), who were examined at theCooper Clinic in Dallas, Texas. To be included,the participant must have had at least twopreventive medicine evaluations between 1987and 1991. Ninety-eight percent of the subjectswere white and 80% were college graduates.Most worked in white collar or professionalpositions. Removed from this group were cur-

rent smokers and subjects with a history ordiagnosis of gastric ulcer, heart attack, stroke,diabetes mellitus, cancer, emphysema, thyroiddiseases, iver diseases,cardiomegaly, abnormalresting or exercise electrocardiogram at the firstor second visit. A total of 2109 subjects (1776men and 333 women) were then available foranalysis.The average interval between the first andsecond visit was 16.7 months (SD: 7.3 months).The medical assessmentwas given after partici-pants gave their informed consent and after theyunderwent at least a 1Zhour fast. Patients wereinstructed to abstain from food, alcohol, andcoffee drinking during the fasting period. Eachvisit consisted of a complete preventive medicalevaluation including a personal and familyhealth history and health habits. All infor-

mation in the medical history questionnaire wasconfidential and served as a reference for thephysician to evaluate and examine the partici-pants health. The same lifestyle questionnairewas used at both the first visit and the secondvisit. Patients were given general health counsel-ing by a physician after medical assessment, utthey were not systematically entered into asupervised lifestyle change program.The questions on coffee consumption in-cluded regular coffee, decaffeinated (or/andherbal) coffee, regular tea, decaffeinated (or/andherbal) tea, and cola with caffeine. Coffee con-sumption was measured as the number of cupsconsumed per week. Changes in coffee con-sumption were calculated using the number ofcups reported in the second visit minus thenumber reported in the first visit.To begin the classification process, threegroups were identified:No consumption-These subjects reported nocoffee, tea, or cola drinking at either the firstor the second visit.New consumer-These subjects reported nodrinking at the first visit but reported drink-ing at the second visit.Quit-These subjects reported drinking at thefirst visit but no drinking at the second visit.

For those who reported drinking coffee atboth the first and second visits, the sample wasfurther divided into three groups:Same consumption-These subjects reportedchanges in drinking habits of not more thanone cup per day.Decreased consumption-These subjects re-ported a decrease n drinking habits of morethan one cup per day.Increased consumption-These subjects reportedan increase in drinking habits of more thanone cup per day.

In addition to the medical history question-naire, a detailed physical activity questionnairewas administered at each visit. Subjects wereasked about their regular exercise activitiesduring the past 3 months. Regular exercise temsincluded jogging or running, walking, treadmillwalking or running, outdoor bicycling, station-ary cycling, swimming laps, aerobic dance orfloor exercise, vigorous racquet sports, andother vigorous sports or exercise.A physical activity index (PAI, energy costs ofhuman physical activities) was calculated inkilocalories per week on the basis of generally

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Coffee Consumption and Cholesterol II91Table I. Selected baseline characteristics (mean + SD) of 2109 non-smokers

Characteristic Men (n = 1776) Women (n = 333)Age (ydTotal cholesterol (mg/dl)HDL cholesterol (mg/dl)Triglyceride (mg/dl)BMI (kg/m*)Diastolic pressure (mmHg)Systolic pressure (mmHg)Glucose (mg/dl)Alcohol consumption (g/wk)PAI (kcal/wk)Consume regular coffee (%)Consume decaffeinated coffee (%)Consume regular tea (%)Consume decaffeinated tea (%)Consume cola with caffeine (%)Regular coffee (cups/wk)*Decaffeinated coffee (cups/wk)*Regular tea (cups/wk)*Decaffeinated tea (cups/wk)*Cola with caffeine (cuos/wk)*

48.1 f 8.6212.2 f 37.350.9 k 13.2100.5 f 60.426.0 + 3. I80.4 + 9.3120.6 k 12.697.6 + 10.193.3 + 113.21588.9 + 1736.363.829.947.410.633.115.3* II.212.6 k 13.98.0 + 7.4

7.0 & 7.46.3 + 6.6

48.8 k 8.7210.5 k 40.066.9 + 15.179.1 f 53.022.8 + 3.775.1 + 8.9112.4 f 13.892.0 f 8.248.9 f 70.51208.0 + 1413.955.334.441.720.226.913.4 f 9.09.8 + 7.48.1 k 9.6

8.6& Il.16.1 +6.1*Consumers only,

accepted MET values in which specific activi-ties, the intensity of those activities, and theirduration were considered [32]. Body mass index(BMI) was calculated in the formula: weight(kg)/height (m). The alcohol content was esti-mated as 1.1 g for 1 oz of beer, 2.7 g for 1 oz ofwine, and 15.1 g for 1 oz of liquor [33].Physical examination methods and pro-cedures followed a standard manual of oper-ations. Fasting lipid and lipoprotein measuresused as outcome variables were measured aspart of the basic physical examination. Totalcholesterol, triglycerides, and high-density lipo-protein (HDL) cholesterol each were measuredusing standardized techniques. Serum totalcholesterol and triglyceride concentration weremeasured using a Technicon Autoanalyzer(Technicon, Tarrytown, NY). Serum HDLcholesterol concentrations were measuredusing an RA 1000 analyzer (Technicon) aftervery-low-density and low-density lipoproteincholesterol were precipitated with sodium phos-photungstate in the presence of magnesiumchloride. Lipid and lipoprotein measurementswere analyzed in a central laboratory that par-

ticipates in the Centers for Disease Control andPrevention Lipid Standardization Program.

RESULTSThe baseline characteristics of subjects,

shown in Table 1, indicate that both men andwomen had similar total cholesterol levels.However, women had more favorable HDLcholesterol and triglyceride levels than men.More men than women reported drinking regu-lar coffee, regular tea, and cola with caffeine;more women then men reported drinking de-caffeinated coffee or tea. Table 2 shows thepercent distribution of daily coffee drinkers bysex among the participants at baseline. Mostcoffee consumers drank between 8 and 21 cupsof regular coffee a week.Table 3 shows the changes in coffee consump-tion. In general, the majority of subjects (over70%) adhered to their original habit. Amongthose who changed their coffee drinking habits,the number of men or women who decreasedtheir regular coffee consumption (by quitting ordecreasing consumption) was almost double the

Item

Table 2. Percent distribution of coffee consumption among 2109 non-smokers at baselineMen Women

cup/week cup/week0 l-7 8-14 15-21 22-28 >28 0 l-7 8-14 15-21 22-28 >28Regular coffee 36.2 18.3 18.9 13.6 6.4 6.6 44.7 15.7 20.5 13.3 3.3 2.4Decaffeinated coffee 70. I 13.1 7.9 4.8 2.3 I.8 65.5 18.0 IO.8 4.2 0.9 0.6Regular tea 52.6 30.6 10.5 4.0 1.3 I.0 58.9 28.8 6.3 4.2 I.2 0.6Decaffeinated tea 89.4 7.8 1.7 0.6 0.2 0.3 79.8 16.0 1.2 0.9 0.6 I.5Cola with caffeine 66.9 26.1 4.2 I.9 0.4 0.5 73.1 21.5 3.0 1.2 1.2 0.0

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1192 Ming Wei et al.Table 3. Percent distribution of changes in coffee, tea and cola among 2109 non-smokers

ItemRegular coffeeDecaffeinated coffeeRegular teaDecaffeinated teaCola with caffeine

Men WomenNever New More Same Less Quit Never New More Same Less Quit30.5 5.1 s.1 37.4 8.0 13 .3 36.3 8.4 3.0 35.1 5.4 11.152.8 17.3 2.3 18.3 3.0 6.3 51.1 14.4 2.7 21.6 2.4 7.8

443.3 9.2 1.8 26.8 2.4 16.5 47.5 11.4 1.8 20.4 3.3 15.680.9 8.6 0.2 4.5 0.6 5.3 69.7 9.9 0.3 12.3 1.2 6.651.6 15.4 0.8 16.7 1.3 14.3 63.1 9.9 0.9 12.6 0.6 12.9

percentage of those who increased their regularcoffee consumption. In contrast, the percentageof men or women who increased their de-caffeinated coffee consumption was almostdouble that of those who decreased their de-caffeinated coffee consumption.The relationship between coffee consumptionand plasma lipid profiles was first examined inthe models with baseline lipid profiles (totalcholesterol, HDL cholesterol, and triglycerides)as dependent variables, and baseline cups ofcoffee drinking as an independent variable. Inthose models, regular coffee consumption wasnot significantly associated with HDL choles-terol or total cholesterol, but was inverselyassociated with triglycerides in men (p = 0.02)(data not shown).Since the cross-sectional analysis cannot indi-cate causality, the relationship between coffeeconsumption and plasma lipid profiles was fur-ther examined in the models with changes inlipid profiles as dependent variables, andchanges in cups of coffee drinking as an inde-pendent variable. In those models, change inregular coffee consumption was significantlyassociated with change in total cholesterol(Table 4). Since the effect of change in de-caffeinated coffee on cholesterol may be ob-

scured by change in regular coffee, we focusedon those who never drank regular coffee, orthose who quit drinking regular coffee, or thosewho decreased heir regular coffee consumptionto explore the relationship between change indecaffeinated coffee and total cholesterol, separ-

ately or together. However, no relationship wasfound between change in decaffeinated coffeeand change in total cholesterol.At this point, all potentially contributingvariables including age, sex, medications, fol-low-up time, baseline and changes in BMI, and20 other lifestyle variables were added to themodels. The only significant relationship foundbetween coffee consumption and lipid profileswas a positive relationship between regularcoffee and total cholesterol in the full modelsand in the final models developed by stepwisebackward analysis (both p c 0.001). Since mostof the baseline variables were not related tochanges n lipid profiles, the majority of baselinevariables were omitted from the model, with theexception of age, sex, BMI, alcohol consump-tion, and PAI. The /I values and significancelevels of changes n coffee, tea, or cola consump-tion related to changes in lipid profiles in therestricted models are shown in Table 4. Acup/week difference in regular coffee ntake wasassociated with approx. 0.3 mg/dl difference intotal cholesterol, or a cup/day difference inregular coffee intake was associated with ap-prox. 2 mg/dl difference in total cholesterol. Thesignificant relationship of regular coffee andtotal cholesterol level was present in both menand women when analyzed separately. No as-sociation between regular coffee consumptionand HDL cholesterol or triglycerides was foundafter adjustment for confounders. When indi-viduals not drinking regular coffee at bothbaseline and follow-up were excluded from

Table 4. Changes in plasma lipid profiles (mg/dl) associated with changes in coffee consumption (cups per week) inregression modelsTotal cholesterol HDL cholesterol Triglycerides

fiu* Pu* fiat Pat fiu Pu /Ia Pa pu Pu pa PaRegular coffee 0.318

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Coffee Consumption and Cholesterol 1193Table 5. Mean baseline and changes n regular coffee (cup/wk), total cholesterol and HDL cholesterol (mg/dl) among regularcoffee groups

Change in TC Change in HDLCBaseline Change Baseline BaselineGroup n coffee in coffee TC Mean Adjusted* HDLC Mean Adjusted*Less 160 27.4 -15.3 219.3 -3.57 -5.34 54.1 -0.92 -0.64Same 783 13.7 -0.29 214.5 -0.14 - 1.39 54.2 -0.92 -0.46More 101 II.0 f 14.6 208.2 +8.93 +J.lO 53.1 -0.16 -0.52Quit 213 13.0 - 13.0 214.0 - 7.12 -6.41 52.2 -1.30 -0.83Never 662 0.0 0.0 201.9 0.0 0.0 52.1 0.0 0.0New 130 0.0 +8.8 205.1 +2.77 +3.32 53.3 - 1.36 -1.29*Adjusted for sex, age, visiting interval, and baseline variables: BMI, alcohol consumption , PAI; and variables of changefrom the first visit to second visit: BMI, alcohol consumption, PAI, regular coffee, decaffeinated coffee, tea, decaffeinatedtea, cola with caffeine, cola without caffeine, meal times, beef, pork, cheese, ried foods, desserts, snacks eggs, butter,hot dogs, fruit, vegetables, skim milk, low-fat milk, whole milk, fried poultry or fish, and baked poultry or fish.

analysis, the relationship between change inregular coffee consumption and change in totalcholesterol remained the same.Further analyses of change in total choles-terol were conducted by using analysis ofvariance and categories of regular coffee con-sumption to replace the continuous variablesindicating changes in coffee consumption.Those not drinking regular coffee at baselineand follow-up were considered as the referencegroup. For total cholesterol, there was a signifi-cant difference among regular coffee groups(p < 0.001). There was an obvious trend (in-crease) in total cholesterol levels among regularcoffee drinking groups who decreased consump-tion, continued at the same consumption, andincreased consumption. Similar trends also ex-isted across the regular coffee groups who quit,who were never regular coffee consumers, andwho started to drink regular coffee (Table 5).There were no significant differences betweenthose who continued to drink at the same leveland those who never drank regular coffee. Nodifferences in HDL cholesterol levels were foundamong any of the regular consumption coffeegroups (p = 0.28).

The correlations between change in regularcoffee consumption and baseline and changes inother variables were estimated. For those witha significance level less than 0.05 in regressionanalysis, we present the results in Table 6 interms of change in regular coffee consumptiongroups. In general, age and baseline butterconsumption were related to an increase inregular coffee consumption, baseline alcoholintake was negatively related to increase inregular coffee consumption. Although thesewho quit drinking regular coffee also improvedother aspects of their lifestyle, only changes inwhole milk use, decaffeinated coffee, and de-

caffeinated tea were consistent among the regu-lar coffee consumption groups (Table 6).

DISCUSSIONIn the present study, there is a statisticallysignificant, positive association between changein regular coffee consumption and change inserum total cholesterol after adjustment for

numerous potential confounders. These resultssupport the hypothesis that consuming regularcoffee may have a deleterious effect on plasmalipid profiles. The results reported here areunlikely to be due to chance because they areconsistent not only with changes in the amountof regular coffee consumed, but also withchanges in regular coffee habits. Regression tothe mean was not an alternative explanation.For example, the baseline total cholesterol wassimilar in the never consumption group and theincreased consumption group. However, theincreased consumption group significantly in-creased a net of 7 mg/dl cholesterol compared tothe never consumption group at endpoint. Thegroups that quit drinking regular coffee orcontinued drinking the same amount were alsosimilar in baseline cholesterol. However, a sig-nificant change (decrease) in total cholesterolwas detected among those who quit drinkingregular coffee compared to those who consumedthe same amount (Table 5).The correlation between serum cholesteroland response to medical advice cannot explainour findings concerning changes in regularcoffee consumption and changes in serumcholesterol. First, if it were true, it might alsoappear in the coffee and HDL cholesterol re-lationship. Second, although those quittingregular coffee improved their lifestyle behaviors,few changes were consistent among regular

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1194 Ming Wei et al.Table 6 . Change in regular coffee intake related to other variables*

BaselineAge WAlcohol (g/wk)Butter (time/wk)

Lessn = 16048.0118.9

I .45

Samen = 78348.699.5

1.88

Moren = 10149.799.8

2.30

Quitn = 27348.388.6

1.52

Nevern = 662

47.357.7I .87

Newn = 13049.696.6

1.00Reg coffee (cup/wk) 27.4 13.7 11.0 13.0 0 0Decaff tea (cup/wk) 0.46 0.69 0.48 0.45 1.40 1.36Decaff coffee (cup/wk) 2.21 2.55 4.72 2.74 5.21 6.03ChangeBMI (kg/m2)PAI (kcal/wk)Alcohol (g/wk)Butter (time/wk)Decaff tea (cup/wk)Decaff coffee (cup/wk)Desert (timejwk)Whole milk (cup/wk)

Lowfat milk (cup/wk)Skin milk (cupiwk)Fry fish (timejwk)Fried food (time/wk)Beef (timelwk)

-0.06260.9-14.10.270.284.230.92-0.51-1.121.000.70-0.46-0.55

-0.07210.0- 12.0-0.120.020.69-0.73-0.15- 1.600.540.452.15-0.35

0.17 -0.41-50.4 406.7-7.22 - 19.90.23 -0.37-0.03 I .07- 1.89 5.08-0.58 -1.370.01 -0.33-0.83 - 1.73 - 1.28 - 1.081.94 1.34 0.93 1.650.14 0.25 0.29-0.28 - 1.04 -0.60-0.26 -1.21 -0.29

-0.20169.7-6.59-0.470.35-0.47-0.72-0.17

-0.03230.1-9.540.78-0.70-0.810.13-0.11

0.15-0.050.07*For all baseline or change variables in regression analysis associated with change in regular coffeeconsumption (p < 0.05,.

coffee consumption groups. Third, the relation-ship between change in regular coffee andchange in total cholesterol was unchanged afteradjustment for differences among coffee drink-ing groups and after controlling for manypotential confounders.

The cream associated with coffee consump-tion is an unlikely explanation for the observedassociation between change in regular coffeeconsumption and change in total cholesterol. Ifthe coffee-cholesterol relation was due to creamadded to the coffee, one might expect that thosewho shifted from regular coffee to decaffeinatedcoffee might still use cream. However, when wefocused on the 433 people who quit or decreasedregular coffee consumption, an increase in de-caffeinated coffee consumption did not appearto have any relationship with change in serumcholesterol.Consistent with the majority of cross-sec-tional and experimental studies, change inserum cholesterol level was not associated withchange in consumption of decaffeinated coffee,tea, and cola with caffeine; and change in HDLcholesterol level was not related to any kind ofcoffee consumption.Some methodological aspects must be con-sidered in our study. Because only two pointestimates were used in the present study,changes over the entire study period may not beprecisely reflected. The random misclassificationmay weaken, rather than strengthen, the re-

lationship. Baseline coffee consumption was notthe same in groups classified by change inregular coffee consumption. However, ouranalysis showed that baseline coffee consump-tion had minimal effect on the changes in serumcholesterol. When changes in BMI and lifestylevariables were considered in the model, therelationship between coffee consumption andserum cholesterol was not altered.

Although the majority of cross-sectional stud-ies found an association between regular coffeeconsumption and total cholesterol, not all stud-ies were consistent. Since 1962, regular coffeeconsumption in the U.S. has fallen 46% whilethe use of decaffeinated coffee has risen 180%[21]. The switch is motivated partly by thewell-documented negative effect of caffeine onthe quality of sleep, and partly by other pur-ported negative effects such as those on thecardiovascular system [28]. Cross-sectionalstudies may underestimate the coffee-cholesterol relationship because some peoplewith high serum cholesterol may tend to reduceconsumption of regular coffee. A few prospec-tive studies using baseline coffee consumption tocorrelate with endpoint serum cholesterol on apopulation basis have been reported [lo]. Ifconsuming a similar dose of coffee has a mini-mal effect on change in total cholesterol, asshown in our study, it might be impossible toinfer a causal relation from those studies. Toour knowledge, this is the first follow-up study

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Coffee Consumption and Cholesterol 1195correlating change in coffee consumption withchange in serum cholesterol in a large group ofmen and women,Results from clinical trials seem to be incon-sistent with regard to regular coffee-cholesterolrelationships. These inconsistencies may be dueto the small sample size of many of thosestudies, the mild effect of regular coffee con-sumption on serum cholesterol levels, the largevariance in lipid profiles, and change in serumcholesterol relating to changes in many otherlifestyle behaviors. Withdrawal syndrome in-cluding headaches, drowsiness, fatigue and de-creases in performance after abrupt cessation ofcoffee consumption has been found in manycaffeine consumers [34], but many experimentalstudies failed to consider changes in potentialconfounding variables. However, Fried et al.,demonstrated that consumption of regularcoffee increased total cholesterol: men whoconsumed 720 ml of regular coffee per dayhad a mean increase in total cholesterol of0.24 mmol/l [31]. Two other experimental stud-ies with small samples (n = 33, n = 42 respect-ively) of hypercholesterolemic men and womenalso found that filter coffee tended to increasetotal serum cholesterol by a similar magnitude(non-significant) [22,24]. The effect magnitudeof regular coffee consumption on cholesterolreported by Fried et al. [31] is almost the sameas our finding: a cup of regular coffee (140 ml)per day was associated with approx. 2 mg/dldifference in total cholesterol. The advantagesof our study include a large sample of men andwomen, consideration of potential confoundingvariables. measurements not only of change incoffee-consumption habits but also of change inamount of coffee consumed, and a relativelyiong follow-up.

CONCLUSIONSWe draw two main conclusions from ourdata. First, our data offer substantial evidencethat there is a linkage between regular coffee

intake and total cholesterol. About 2-3 mg/dlnet increase in total cholesterol was associatedwith an increase of one cup of regular coffee perday. Although the implication for coronaryheart disease risk of the coffee-induced increasesin serum cholesterol appears mild, quitting orreducing regular coffee consumption still hasclinical meaning for patients with high serumcholesterol who are heavy coffee consumers.Since no relationship between decaffeinated

coffee and serum cholesterol levels was found, ashift from regular coffee to decaffeinated coffeemay improve serum cholesterol profiles in thepopulation. Second, we find no accumulatingeffect of coffee consumption on serum choles-terol. The changes in total cholesterol levelsamong persons who do not consume regularcoffee and among these continuing the samedose of regular coffee were basically the same.Clearly, it is not necessary to suggest that thosewith moderate regular coffee consumption andnormal cholesterol levels change their coffeeconsumption habit for serum cholesterolreasons.Acknowledgemenrs-This work was supported in part byGrant #AG-06945 from the National Institutes of Health.The authors wish to thank the Cooper Clinic physicians andtechnicians. The authors also wish to thank Dorothy Davisfor her help.

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