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ORIGINAL CONTRIBUTION
Fruit and Vegetable Intake in Relation to
Risk of Ischemic Stroke
Kaumudi J. Joshipura, ScD
Alberto Ascherio, MD
JoAnn E. Manson, MD
Meir J. Stampfer, MD
Eric B. Rimm, ScD
Frank E. Speizer, MD
Charles H. Hennekens, MD
Donna Spiegelman, ScD
Walter C. Willett, MD
IN SEVERAL ARTICLES,NUTRIENTS IN
fruit and vegetables such as di-
etary fiber, potassium, and antioxi-
dants have been associated with re-
duced risk of cardiovascular disease
(CVD).1-5 However, the data directly
relating fruit and vegetable intake and
CVD are sparse, as summarized in a re-
cent review,6and the results of studies
that specifically examined fruit and
vegetables as a group were inconsis-
tent.6Furthermore, many studies were
small with few end points, dietary as-
sessments were often crude and avail-
able only at baseline, and the distinc-
tion was often not made between
hemorrhagic and ischemic strokes,
which have different causes. To under-
stand better the relationship between
diet and stroke, we examined intakes
of specific fruits and vegetables, as well
as overall fruit and vegetable consump-
tion, in relation to the incidence of is-
chemic stroke in 2 large cohorts of
women and men.
METHODS
Study Populations
Data for this analysis were derived from
2 ongoing cohorts, the Nurses’ Health
Study (NHS)7and the Health Profession-
als’ Follow-up Study (HPFS).1The 2
studies are similar in design; participants
in both cohorts have been completing
mailed questionnaires every 2 years to
provide information on medical history,
health behaviors, and the occurrence of
cardiovascular and other outcomes. The
NHS enrolled 121 700 female registered
nurses aged 30 to 55 years in 1976.
The HPFS study population is com-
posed of 51 529 male health profession-
als including dentists, veterinarians,
pharmacists, optometrists, osteopathic
physicians, and podiatrists who were 40
to 75 years of age in 1986.
Population for Analysis
After 4 mailings, 98 462 women re-
turned the 1980 NHS dietary question-
Author Affiliations: Departments of Epidemiology (Drs
Joshipura, Ascherio, Manson, Stampfer, Rimm, Spiegel-
man, and Willett), Nutrition (Drs Ascherio, Stampfer, Rimm,
and Willett), Environmental Health (Dr Speizer), and Bio-
statistics (Dr Spiegelman), Harvard School of Public Health;
Department of Oral Health Policy and Epidemiology
(Dr Joshipura), Harvard School of Dental Medicine;
Channing Laboratory (Drs Stampfer, Rimm, Speizer, and
Willett) and the Division of Preventive Medicine (Dr
Manson), Department of Medicine, Brigham and Wom-
en’s Hospital, Harvard Medical School, Boston, Mass.
Dr Hennekens now resides in Boca Raton, Fla.
Corresponding Author and Reprints: Kaumudi J. Joshi-
pura, ScD, Department of Oral Health Policy and
Epidemiology, Harvard School of Dental Medicine,
188 Longwood Ave, Boston, MA 02115 (e-mail:
hpkaj@gauss.med.harvard.edu).
Context Few studies have evaluated the relationship between fruit and vegetable
intake and cardiovascular disease.
Objective To examine the associations between fruit and vegetable intake and is-
chemic stroke.
Design, Setting, and Subjects Prospective cohort studies, including 75 596 women
aged 34 to 59 years in the Nurses’ Health Study with 14 years of follow-up (1980-
1994), and 38 683 men aged 40 to 75 years in the Health Professionals’ Follow-up
Study with 8 years of follow-up (1986-1994). All individuals were free of cardiovas-
cular disease, cancer, and diabetes at baseline.
Main Outcome Measure Incidence of ischemic stroke by quintile of fruit and veg-
etable intake.
Results A total of 366 women and 204 men had an ischemic stroke. After control-
ling for standard cardiovascular risk factors, persons in the highest quintile of fruit and
vegetable intake (median of 5.1 servings per day among men and 5.8 servings per
day among women) had a relative risk (RR) of 0.69 (95% confidence interval [CI],
0.52-0.92) compared with those in the lowest quintile. An increment of 1 serving per
day of fruits or vegetables was associated with a 6% lower risk of ischemic stroke (RR,
0.94; 95% CI, 0.90-0.99; P= .01, test for trend). Cruciferous vegetables (RR, 0.68 for
an increment of 1 serving per day; 95% CI, 0.49-0.94), green leafy vegetables (RR,
0.79; 95% CI, 0.62- 0.99), citrus fruit including juice (RR, 0.81; 95% CI, 0.68-0.96),
and citrus fruit juice (RR, 0.75; 95% CI, 0.61-0.93) contributed most to the apparent
protective effect of total fruits and vegetables. Legumes or potatoes were not asso-
ciated with lower ischemic stroke risk. The multivariate pooled RR for total stroke was
0.96 (95% CI, 0.93-1.00) for each increment of 2 servings per day.
Conclusions These data support a protective relationship between consumption of
fruit and vegetables—particularly cruciferous and green leafy vegetables and citrus
fruit and juice—and ischemic stroke risk.
JAMA. 1999;282:1233-1239 www.jama.com
See also Patient Page.
© American Medical Association. All rights reserved. JAMA, October 6, 1999—Vol 282, No. 13 1233
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naire. We excluded those with 10 or
more items blank, those with implau-
sible scores for total food intake (,2092
kJ/d or .14 644 kJ/d) (n = 5994), and
those with previously diagnosed can-
cer, diabetes, or CVDs (n = 7254).
Among the men, we excluded 6442 par-
ticipants who reported CVD, cancer, or
diabetes prior to the follow-up period.
We further excluded 1349 men who re-
ported daily energy intake outside the
plausible range of 3360 to 17 640 kJ/d
or who left 70 or more of the 131 di-
etary questions blank. More than 90%
of the baseline population, on aver-
age, responded to at least 1 follow-up
questionnaire, and about 80% com-
pleted each of the repeated dietary ques-
tionnaires during follow-up in these co-
horts. The total number of subjects
included in this analysis were 75 596
women and 38 683 men (TABLE 1).
Assessment of Stroke End Points
Participants (or next of kin for the
deceased) reporting an incident stroke
on a follow-up questionnaire were asked
permission to have their medical records
reviewed. Using these records, includ-
ing imaging results recommended by
the National Survey of Stroke,8we sub-
classified the strokes into ischemic
(embolic or thrombotic), hemorrha-
gic (subarachnoid or intracerebral), or
unknown type. Cases attributed to
infections or malignant processes or
cases of indeterminate age discovered
on computed tomographic or mag-
netic resonancing imaging scans with-
out acute symptoms were not included.
Physicians reviewing the medical
records were unaware of the partici-
pants’ dietary status. Deaths were
reported by next of kin or coworkers
or were obtained from postal authori-
ties or from the National Death Index.
Only strokes confirmed by medical
records were included in this analysis.
We considered nonresponders who
were not listed on the National Death
Index as noncases.
Table 1. Description of Age-Standardized Cardiovascular Risk Factors by Baseline Quintiles of Fruit and Vegetable Intake Among 75 596
Women and 38 683 Men*
Fruit Quintiles Vegetable Quintiles
135135
Women
Servings per day 0.9 2.3 4.5 1.6 3.3 6.2
Age, y 44.6 46.2 47.4 45.5 45.9 47.0
Current smoker, % 42.8 25.9 19.8 32.1 28.5 25.5
Current estrogen replacement, %† 6.3 6.7 7.1 6.9 6.6 6.6
Regular vigorous activity, % 34.2 46.2 54.2 37.9 44.0 53.5
Body mass index, kg/m224.2 24.3 24.3 24.2 24.3 24.4
History at baseline, %
Hypertension 13.2 14.8 17.1 14.2 15.1 15.9
High cholesterol level 5.1 4.7 5.4 4.4 4.9 5.7
Parents’ coronary heart disease history
at age #65 y, %
20.0 20.5 20.3 19.4 20.0 21.2
Multivitamin supplement use, % 27.6 34.5 38.7 30.8 33.0 37.3
Saturated fat, g/d 26.7 27.3 28.7 24.7 27.6 29.7
Cereal fiber, g/d 2.3 2.7 2.9 2.4 2.7 2.8
Men
Servings per day 0.7 2.1 4.3 1.4 2.8 5.4
Age, y 51.5 54.1 55.2 53.0 53.7 54.6
Current smoker, % 18.4 8.6 4.9 13.0 10.0 7.0
Physical activity, metabolic equivalent/wk‡ 14.1 19.7 26.5 16.0 19.2 24.9
Body mass index, kg/m225.7 25.4 25.2 25.5 25.4 25.5
History at baseline, %
Hypertension 19.3 19.3 19.6 19.0 20.0 20.0
High cholesterol level 9.2 9.7 11.8 9.0 11.0 11.0
Family history of coronary heart disease at age ,60 y, % 12.0 12.0 12.0 11.0 12.0 13.0
Multivitamin supplement use, % 41.2 48.4 54.1 45.0 46.0 52.0
Saturated fat, g/d 24.3 24.7 24.9 22.6 25.0 26.1
Cereal fiber, g/d 5.6 7.1 8.1 5.9 7.0 7.9
*Standardized for age (except for age itself) to the cohort age distribution (Nurses’ Health Study or Health Professionals’ Follow-up Study); values are means unless otherwise
specified.
†Among postmenopausal women only.
‡Metabolic equivalent (MET) hours = sum of the average time per week spent in each activity 3MET value of each activity
MET value = caloric need/kg body weight/hour activity
caloric need/kg body weight/hour at rest
FRUIT AND VEGETABLE INTAKE AND ISCHEMIC STROKE
1234 JAMA, October 6, 1999—Vol 282, No. 13 ©1999 American Medical Association. All rights reserved.
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Dietary Assessment
In the NHS, diet was assessed in 1980,
1984, 1986, and 1990. A 61-item semi-
quantitative food frequency question-
naire (FFQ) including 6 fruit and 11 veg-
etable items, and potatoes was included
in 1980. An expanded 116-item FFQ in-
cluding 15 fruit items, 28 vegetable
items, and potatoes were included in
1984; similar questionnaires were re-
peated in 1986 and 1990. In the HPFS,
diet was assessed in 1986 and 1990 us-
ing an expanded semiquantitative FFQ
similar to that used in the NHS. Fur-
ther details about the NHS and the HPFS
have been described elsewhere.1,7
On dietary questionnaires, partici-
pants reported their average intake of
a specified portion size for each food
over the past year. For each food item
on the questionnaire, 9 responses were
possible, ranging from never or less than
once per month to 6 or more times per
day. Detailed descriptions of the repro-
ducibility and validity of the FFQ for
both men and women have been pub-
lished previously.9-11 Validity of the di-
etary data has been documented by
comparisons with multiple weighted di-
etary records correcting for within-
person weekly variation in diet. The
correlation coefficients for responses to
the 61-item questionnaire in the NHS
for fruits and vegetables compared with
four 1-week diet records averaged 0.57
(ranging from 0.27-0.93). In the HPFS,
Pearson correlations between intake
from the questionnaire and the diet
records, corrected for within-person
weekly variation in diet record, were on
average approximately 0.7 for intake of
individual fruits and 0.5 for intake of
individual vegetables.
Responses to the individual food
items were converted to average daily
intake of each fruit and vegetable item
for each participant. The average daily
intakes of individual food items were
combined to compute total fruit and
vegetable intake, as well as intakes of
composite fruit and vegetable groups.
The definitions of composite groups
were based on a report by Steinmetz et
al12; the groups were modified to re-
late to our questionnaires and hypoth-
esis (available on request from the au-
thors). Vitamin C–rich fruits and
vegetables included items containing
more than 30 mg of vitamin C per serv-
ing. For total vegetable intake, we did
not include potatoes, tofu and soy-
beans, dried beans and lentils, or items
with small portion sizes such as chili
sauce and garlic. Missing individual
components were counted as zero in-
take when aggregating items to com-
pute the composite items.
Data Analyses
We recorded 670 total strokes among
women: 366 new cases of ischemic
stroke, 198 new cases of hemorrhagic
stroke, and 106 of unknown type. There
were 317 total strokes among men: 204
ischemic, 64 hemorrhagic, and 49 of
unknown type. Due to the relatively
small number of cases of hemorrhagic
stroke to date and the differences in
cause between ischemic and hemor-
rhagic stroke, this article focuses only
on ischemic stroke.
Person-time for each participant was
calculated from the date of return of the
1980 questionnaire (in the NHS) or the
1986 questionnaire (in the HPFS) to the
earlier of the date of first stroke event,
death, or the cutoff date (June 1, 1994,
for the NHS, and January 31, 1994, for
the HPFS). Participants who reported
CVD or cancer or diabetes prior to
completion of the baseline dietary ques-
tionnaires were excluded. Each partici-
pant thus contributed only 1 end point,
and the cohort at risk for each fol-
low-up period included only those who
remained free from stroke at the begin-
ning of each 2-year follow-up period.
Due to the difference in sex, fol-
low-up time, and the questionnaires in
the 2 cohorts, the analyses were per-
formed separately in each cohort and
combined to achieve better control of
confounding. The risk for ischemic
stroke was compared by fruit/vegetable
intake using pooled logistic regression
methods proposed by Cupples et al13 and
D’Agostino et al,14 which summarize the
relative risk (RR) across all 2-year fol-
low-up periods. Analyses were adjusted
for age (5-year categories); smoking
(never, former, current: 1-14, 15-24, and
$25 cigarettes per day); alcohol con-
sumption (5 categories in women, 7 cat-
egories in men); family history of myo-
cardial infarction (,65 years of age in
women, ,60 years of age in men); body
mass index (quintiles); multivitamin
supplement use; vitamin E use, aspirin
use, physical activity (2 categories in
women, quintiles in men); and reported
hypertension and hypercholesterol-
emia and time period. Additionally,
among the women, we controlled for
postmenopausal hormone use. We also
controlled for total energy intake.15,16
Because of the long follow-up period,
exposures and confounders were
updated to better represent long-term
dietary patterns.17 In the NHS we used
the 1980, 1984, 1986, and 1990 ques-
tionnaires, and in the HPFS we used the
1986 and 1990 questionnaires. We com-
puted fruit and vegetable intake for each
follow-up period as a cumulative aver-
age of intake from all available FFQs up
to the start of the 2-year follow-up
period in which events were reported.
Since intermediate end points may influ-
ence diet, in cases in which the partici-
pant experienced angina, coronary
artery bypass grafting or angioplasty,
hypercholesterolemia, hypertension, or
diabetes, we stopped updating diet at
the beginning of the interval in which
they experienced the outcome.
The average daily intake for each com-
posite item was coded into quintiles of
intake within each cohort. Each quin-
tile of intake was compared with the low-
est quintile of intake. Trends in stroke
risk across individual fruits and veg-
etables and composite items were as-
sessed in logistic models by using a vari-
able for the average number of servings
consumed per day. To assess the trend
for composite items, we used the me-
dian values of intake for each quintile
of the composite item to minimize the
influence of outliers. The RR for the con-
tinuous measures, for both the indi-
vidual and composite items, indicates the
increase or decrease in risk associated
with an average increment of 1 serving
per day of the standard portion size de-
fined in the questionnaires.
FRUIT AND VEGETABLE INTAKE AND ISCHEMIC STROKE
©1999 American Medical Association. All rights reserved. JAMA, October 6, 1999—Vol 282, No. 13 1235
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Because a protective effect of fruits and
vegetables could be explained by their
vitamin content, we also evaluated asso-
ciations between fruit and vegetables and
ischemic stroke separately among mul-
tivitamin supplement users and nonus-
ers. Nonusers of multivitamins who took
other vitamin supplements at baseline
were excluded from these subgroup
analyses. Nonusers from the HPFS who
took mineral supplements at baseline
were also excluded from the subgroup
analyses; data on mineral supplements
were not available in the NHS in 1980.
We also performed the analyses sepa-
rately for current smokers and for never
or past smokers to determine if smok-
ing influenced the association between
intake of fruits and vegetables and ische-
mic stroke. For the primary analyses, the
RR from the (pooled) logistic regres-
Table 2. Multivariate Relative Risks (RRs) of Ischemic Stroke With 95% Confidence Intervals (CIs) by Quintile and per Serving per Day*
Composite Items
Quintile†
1 Serving
per Day‡
Median Servings
per Day§
2345 Overall
[Quintile
1, 5]
All fruits and vegetables
Women 0.89 (0.66-1.20) 0.75 (0.55-1.04) 0.60 (0.42-0.85) 0.74 (0.52-1.05) 0.93 (0.87-1.00) 5.82 [2.93, 10.15]
Men 0.77 (0.49-1.20) 0.70 (0.44-1.10) 1.03 (0.67-1.57) 0.61 (0.37-1.00) 0.96 (0.89-1.03) 5.07 [2.54, 9.15]
Pooled 0.85 (0.66-1.09) 0.73 (0.56-0.95) 0.77 (0.46-1.31) 0.69 (0.52-0.92) 0.94 (0.90-0.99)
All fruits
Women 0.88 (0.65-1.20) 0.82 (0.60-1.13) 0.66 (0.47-0.93) 0.69 (0.49-0.98) 0.87 (0.78-0.96) 2.33 [0.86, 4.54]
Men 0.78 (0.50-1.22) 0.84 (0.54-1.31) 0.87 (0.56-1.34) 0.68 (0.42-1.10) 0.93 (0.82-1.05) 2.09 [0.72, 4.33]
Pooled 0.85 (0.66-1.09) 0.83 (0.64-1.07) 0.73 (0.56-0.96) 0.69 (0.52-0.91) 0.89 (0.82-0.97)
All vegetables
Women 1.23 (0.92-1.65) 0.88 (0.63-1.22) 0.76 (0.54-1.08) 0.89 (0.63-1.26) 0.95 (0.86-1.06) 3.34 [1.60, 6.21]
Men 0.99 (0.65-1.51) 0.76 (0.49-1.20) 0.81 (0.51-1.26) 0.90 (0.58-1.41) 0.98 (0.88-1.09) 2.83 [1.36, 5.37]
Pooled 1.15 (0.90-1.46) 0.84 (0.64-1.09) 0.78 (0.59-1.03) 0.90 (0.68-1.18) 0.96 (0.89-1.04)
Total citrus fruits
Women 0.70 (0.51-0.96) 0.82 (0.60-1.10) 0.72 (0.52-0.98) 0.59 (0.42-0.82) 0.75 (0.62-0.91) 0.85 [0.08, 1.80]
Men 1.24 (0.80-1.92) 0.92 (0.59-1.45) 0.92 (0.59-1.44) 0.92 (0.59-1.44) 0.93 (0.73-1.18) 0.86 [0.08, 1.88]
Pooled 0.91 (0.52-1.60) 0.85 (0.66-1.09) 0.78 (0.60-1.01) 0.72 (0.47-1.11) 0.81 (0.68-0.96)
Citrus fruit juices
Women 0.80 (0.58-1.11) 0.77 (0.56-1.05) 0.91 (0.66-1.25) 0.61 (0.45-0.84) 0.73 (0.56-0.95) 0.43 [0.00, 1.00]
Men 0.91 (0.60-1.39) 0.84 (0.54-1.31) 0.85 (0.53-1.37) 0.74 (0.49-1.13) 0.80 (0.57-1.13) 0.43 [0.00, 1.00]
Pooled 0.84 (0.65-1.09) 0.79 (0.61-1.02) 0.89 (0.68-1.16) 0.65 (0.51-0.84) 0.75 (0.61-0.93)
Cruciferous vegetables
Women 1.09 (0.80-1.50) 1.04 (0.77-1.42) 0.91 (0.65-1.26) 0.77 (0.54-1.08) 0.69 (0.44-1.08) 0.42 [0.14, 0.95]
Men 0.65 (0.42-0.99) 0.82 (0.54-1.23) 0.69 (0.45-1.05) 0.64 (0.42-0.99) 0.70 (0.43-1.14) 0.04 [0.14, 1.01]
Pooled 0.86 (0.51-1.44) 0.95 (0.74-1.22) 0.82 (0.63-1.06) 0.71 (0.55-0.93) 0.68 (0.49-0.94)
Green leafy vegetables
Women 0.65 (0.46-0.91) 0.71 (0.52-0.96) 0.77 (0.56-1.06) 0.76 (0.55-1.05) 0.84 (0.61-1.15) 0.73 [0.16, 1.51]
Men 1.01 (0.67-1.52) 1.08 (0.70-1.67) 0.76 (0.49-1.17) 0.76 (0.48-1.20) 0.73 (0.52-1.03) 0.59 [0.16, 1.36]
Pooled 0.80 (0.51-1.24) 0.85 (0.57-1.27) 0.77 (0.59-0.99) 0.76 (0.58-0.99) 0.79 (0.62-0.99)
Vitamin C–rich fruits and vegetables
Women 0.83 (0.62-1.12) 0.73 (0.54-1.00) 0.68 (0.49-0.95) 0.64 (0.46-0.89) 0.80 (0.68-0.93) 1.53 [0.54, 3.08]
Men 0.82 (0.52-1.27) 0.62 (0.39-0.99) 1.00 (0.66-1.51) 0.77 (0.49-1.20) 0.95 (0.80-1.13) 1.42 [0.46, 2.96]
Pooled 0.83 (0.64-1.06) 0.70 (0.54-0.90) 0.81 (0.56-1.17) 0.68 (0.52-0.89) 0.87 (0.73-1.03)
Legumes
Women 1.15 (0.83-1.60) 1.01 (0.71-1.44) 1.38 (1.02-1.88) 1.16 (0.83-1.63) 1.65 (0.81-3.40) 0.16 [0.00, 0.43]
Men 0.83 (0.55-1.25) 0.98 (0.62-1.54) 1.07 (0.71-1.62) 0.85 (0.54-1.34) 0.71 (0.33-1.52) 0.22 [0.00, 0.57]
Pooled 1.00 (0.73-1.38) 1.00 (0.75-1.32) 1.26 (0.98-1.62) 1.03 (0.77-1.39) 1.09 (0.47-2.51)
Potatoes
Women 0.96 (0.61-1.52) 0.92 (0.61-1.39) 1.12 (0.74-1.72) 1.09 (0.69-1.72) 1.15 (0.69-1.90) 0.43 [0.14, 0.96]
Men 1.11 (0.81-1.52) 1.10 (0.81-1.50) 1.04 (0.74-1.46) 1.23 (0.88-1.72) 1.25 (0.85-1.83) 0.51 [0.14, 1.02]
Pooled 1.06 (0.82-1.37) 1.03 (0.80-1.32) 1.07 (0.82-1.40) 1.18 (0.90-1.54) 1.21 (0.89-1.64)
*Results in men, women, and pooled data for quintiles of intake compared with the lowest quintile and for an increment of 1 serving per day. Person-years = 581 118 among women
and 166 566 among men; cases = 366 among women and 204 among men. Models are adjusted for age (5-year categories), smoking (never, former, current: 1-14, 15-24, $25
cigarettes per day), alcohol (7 categories in men, 5 categories in women), family history of myocardial infarction (age ,60 y in men and age ,65 y in women), body mass index
(quintiles), vitamin supplement use, vitamin E use, physical activity, aspirin use, 7 time periods for women, 4 time periods for men, hypertension and hypercholesterolemia, total
energy intake, and among women, postmenopausal hormone use.
†Reference is quintile 1, lowest intake.
‡Continuous variable for increments of 1 serving per day using median value for the quintile of intake.
§Distribution based on 1986 questionnaires.
FRUIT AND VEGETABLE INTAKE AND ISCHEMIC STROKE
1236 JAMA, October 6, 1999—Vol 282, No. 13 ©1999 American Medical Association. All rights reserved.
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sion pooling across 2-year time periods
from the 2 cohorts were further com-
bined using the pooling methods pro-
posed by DerSimonian and Laird18 that
weighted the RR in each cohort by the
inverse of the SEs. Finally, we exam-
ined the adjusted RR for total stroke,
using methods similar to those used for
ischemic stroke.
RESULTS
Table 1 shows the distribution of the
baseline standard cardiovascular risk fac-
tors by quintiles of baseline fruit and veg-
etable intake from the NHS and the
HPFS (quintile 5 being the highest in-
take group). Persons who consumed
more fruit and vegetables were older and
generally had healthier lifestyles as in-
dicated by lower rates of smoking and
higher levels of physical activity. Simi-
lar trends were seen with other behav-
ioral variables. Smoking and exercise
were more strongly related to fruit in-
take compared with vegetables. In-
takes of protein, cereal fiber, transfatty
acids, saturated fat, polyunsaturated fat,
and cholesterol increased with increas-
ing fruit and vegetable intake.
Median intakes of total fruits and veg-
etables in 1986 were 5.8 servings per day
for women (2.9 and 10.2 for quintiles 1
and 5, respectively) and 5.1 servings per
day for men (2.6 and 9.2 for quintiles 1
and 5, respectively) (TABLE 2). Results
from both studies individually, as well
as pooled analyses for composite fruit
and vegetable items, are presented in
Table 2. Overall fruit and vegetable
intake was inversely related to risk of
ischemic stroke after adjusting for poten-
tial confounders. Those in the top quin-
tile of intake had an RR of 0.69 (95% CI,
0.52-0.92) compared with those in the
lowest quintile; the corresponding RR
was 0.74 (95% CI, 0.52-1.05) among
women and 0.61 (95% CI, 0.37-1.00)
among men. Assessed as a continuous
trend, an increment of 1 serving per day
was associated with a 7% lower risk
among women and a 4% lower risk am-
ong men; for the combined population
there was a 6% lower risk of ischemic
stroke (P= .01, test for trend). Similar
results were seen for total fruit and for
total vegetables separately. Additional
control for intakes of transfatty acids,
saturated fat, polyunsaturated fat, or cho-
lesterol did not appreciably alter the
results. All the composite items except
legumes and potatoes were inversely
associated with risk of ischemic stroke.
The lowest risks were observed for high
consumption of cruciferous vegetables
(eg, broccoli, cabbage, cauliflower, brus-
sel sprouts), green leafy vegetables, cit-
rus fruits, and vitamin C–rich fruit and
vegetables. The results were similar across
both cohorts, especially the measures of
trend. Again, additional analyses incor-
porating nutrients that may be potential
confounders including protein, cereal fi-
ber, saturated fat, transfatty acids, poly-
unsaturated fat and cholesterol intake, or
meat intake did not change the results.
For example, when meat intake was
added to the model, the RR for a 1 serv-
ing per day increment of total fruits and
vegetables changed from 0.94 (95% CI,
0.90-0.99) to 0.95 (95% CI, 0.90-0.99);
addition of transfatty acid quintiles re-
sulted in an RR of 0.94 (95% CI, 0.90-1.0).
When we examined total stroke as the
outcome, an increment of 1 serving per
day of total fruits and vegetables was
associated with a 3% lower risk among
women and a 5% lower risk among men;
the multivariate pooled RR was 0.96 (95%
CI, 0.93-1.00). Results for specific fruits
and vegetables were in the same direction
as for ischemic stroke or null.
The FIGURE shows the multivariate
RRs and 95% CIs for ischemic stroke
computed for increasing servings per
day of intake of fruit and vegetables
(pooled for the NHS and the HPFS),
suggesting a decreasing risk of ische-
mic stroke with increasing intake. There
was no apparent further reduction in
risk beyond 6 servings per day.
Supplementusersconsumedmore fruit
and vegetables than nonusers (6.08 serv-
ings per day vs 5.64 servings per day
among women and 5.40 servings per day
vs 4.94 servings per day among men).
Similarly, nonsmokers consumed more
fruit and vegetables than current smok-
ers (6.00 servings per day vs 5.10 serv-
ings per day among women and 5.21 serv-
ings per day vs 4.21 servings per day
among men). Pooled RRs for an incre-
ment of 1 serving per day (linear trend)
by multivitamin supplement use or non-
use and by smoking status are present-
ed in TABLE 3. The inverse associations
between consumption of fruits, citrus
fruit, and cruciferous vegetables and risk
of ischemic stroke were somewhat stron-
ger in the nonsupplement group com-
pared with the supplement user group.
Although the associations were somewhat
weaker and not statistically significant
among multiple vitamin users, the num-
ber of cases was smaller and the CIs in-
cluded substantial reductions in risk. No
striking differences in associations were
seen by smoking status, although the ap-
parent protective effects appeared to be
slightly stronger among current smok-
ers than among past and never smokers.
The CIs indicate that interactions between
intake of fruit and vegetables and smok-
ing (or supplement use) or ischemic
stroke are not significant.
Analyses of individual fruit and veg-
etable items that constituted the com-
posite items did not show any single
fruit or vegetable that was strikingly
Figure. Total Fruit and Vegetable Intake and
Risk of Ischemic Stroke
1.2
1.0
0.8
0.6
0.4
0.2
0
<3 3-3.9 6-7.95-5.94-4.9 ≥8
Fruit and Vegetable Intake (Servings per Day)
RR and 95% CI
Pooled multivariate relative risks (RRs) of ischemic
stroke with 95% confidence intervals (CIs) for men
and women for increasing intake of total fruits and
vegetables. Data are for men and women combined,
controlled for the same factors as in Table 2, with none
to less than 3 servings per day as the comparison group.
FRUIT AND VEGETABLE INTAKE AND ISCHEMIC STROKE
©1999 American Medical Association. All rights reserved. JAMA, October 6, 1999—Vol 282, No. 13 1237
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more protective than others. Most items
showed null or inverse associations. In
general, the findings were consistent
with what may be expected from the
composite analyses (data not shown).
COMMENT
Overall, these findings support a pro-
tective effect between consumption of
fruits and vegetables against risk of is-
chemic stroke in both women and men.
Fruit and vegetables—in particular cru-
ciferous and green leafy vegetables, cit-
rus fruits, and citrus fruit juices—
were inversely associated with risk of
ischemic stroke in both cohorts. Fruit
and vegetable intake was associated
with behavioral risk factors such as
smoking and exercise. However, ad-
justment for behavioral and other risk
factors, including nutrients that were
suspected to be confounders, did not
explain the apparent benefits of higher
fruit and vegetable consumption, al-
though adjustments for these factors did
attenuate the observed associations.
These cohorts of health profession-
als tended to have healthier lifestyles than
the general population; for example, the
median intake of fruit and vegetables in
these cohorts was over the recommended
5 servings per day.19,20 The existence of
a dose-response relationship within these
groups, which are relatively homogenous
in occupation and education, is particu-
larly notable, as confounding by variables
related to socioeconomic status is mini-
mized. We found that intake beyond 6
servings per day provided little further
reduction in risk of ischemic stroke com-
pared with intake of 5 to 6 servings per
day. These findings lend support to the
recommendation of eating 5 servings per
day of fruit and vegetables. For specific
fruits and vegetables, the RRs for an in-
crement of 1 serving per day should be
interpreted in light of the consumption
level. For example, the intake of legumes
was very low, with only 0.5 servings per
day as the median intake in the highest
quintile (Tables 2 and 3); hence, our abil-
ity to study the effect of higher consump-
tion was limited.
Our results are similar to a study of
832 men from the Framingham co-
hort. The RR of 0.94 in our study for an
increment of 1 serving per day trans-
lates to a decremental risk of 0.83 for 3
servings per day, which is reasonably
comparable with the RR of 0.75 for is-
chemic stroke (95% CI, 0.55-1.03) for
an increment of 3 servings per day of
fruit and vegetables (including pota-
toes)21 in the Framingham study. No as-
sociation between green and yellow veg-
etables and total stroke was observed
among a 16-year follow-up of 265 118
Japanese people,22 but the study re-
ported on total strokes and the major-
ity of strokes in Japan at that time were
likely to be hemorrhagic. In a 5-year fol-
low-up23 of 1299 Massachusetts nurs-
ing home residents, the RR for stroke
was 0.40 for carrots (95% CI, 0.17-
0.98) and 0.49 for salads (95% CI, 0.31-
0.71), comparing 1 or more vs less than
1 serving per day, which is stronger than
comparable associations in our study.
The constituents of fruits and veg-
etables potentially responsible for their
apparent beneficial effects on risk of is-
chemic stroke include potassium, fo-
late, and fiber; the associations be-
tween ischemic stroke and these
nutrients have been evaluated in other
reports.23-27 Dietary flavonoids (which
are present in fruits and vegetables) have
also been recently related to decreased
risk of ischemic stroke.28 There is little
evidence relating dietary fiber to stroke.
The evidence for potassium is limited
and most studies were based on a 24-
hour recall, which may not be able to ad-
just for other foods and nutrients that
could explain the inverse associations re-
ported.4,24 However, in a recent report
based on the same cohort of men in-
cluded in these analyses,25 a significant
inverse association was seen (multivar-
iate RR, 0.62; 95% CI, 0.43-0.88 com-
paring the top and bottom quintile of po-
tassium intake). The evidence for folate
is largely indirect through its effect on
homocysteine,26 although in the
Framingham Heart Study, an associa-
tion was observed between low serum
concentrations and low intakes of fo-
late and increased risk of extracranial ca-
rotid artery stenosis.27 Hence, the evi-
dence for a protective role of any single
constituent of fruits and vegetables is
suggestive but inconclusive, and it is im-
portant to consider the role of fruits and
Table 3. Multivariate Relative Risks (RRs) and 95% Confidence Intervals (CIs) for Ischemic
Stroke for 1 Serving per Day by Multivitamin Use and Smoking Status*
No Vitamin
Supplement
(n = 295)
Multivitamin
Supplement
(n = 216)
Never and
Past Smokers
(n = 388)
Current
Smokers
(n = 172)
All fruits and
vegetables
0.93 (0.87-0.99) 0.98 (0.91-1.05) 0.96 (0.91-1.02) 0.93 (0.78-1.10)
All fruits 0.90 (0.76-1.05) 0.96 (0.84-1.09) 0.94 (0.85-1.03) 0.86 (0.70-1.06)
All vegetables 0.91 (0.81-1.03) 0.96 (0.85-1.08) 0.97 (0.89-1.06) 0.86 (0.74-1.02)
Total citrus fruits 0.77 (0.62-0.97) 0.86 (0.61-1.23) 0.88 (0.74-1.05) 0.88 (0.48-1.63)
Citrus fruit juices 0.72 (0.53-0.97) 0.90 (0.63-1.26) 0.78 (0.60-1.01) 0.70 (0.47-1.04)
Cruciferous vegetables 0.55 (0.34-0.91) 0.87 (0.52-1.43) 0.66 (0.45-0.98) 0.57 (0.28-1.16)
Green leafy vegetables 0.78 (0.56-1.09) 0.81 (0.56-1.17) 0.74 (0.56-0.98) 0.91 (0.58-1.43)
Vitamin C–rich fruits
and vegetables
0.83 (0.66-1.04) 0.89 (0.74-1.08) 0.88 (0.77-1.01) 0.73 (0.58-0.93)
Legumes 1.40 (0.48-4.09) 0.85 (0.36-1.98) 1.05 (0.56-1.98) 1.58 (0.58-4.29)
Potatoes 1.18 (0.72-1.94) 1.12 (0.68-1.85) 1.17 (0.80-1.70) 1.35 (0.79-2.31)
Women
Person-years 324 869 196 788 449 006 129 324
Cases 214 122 226 139
Men
Person-years 78 171 69 397 144 125 15 903
Cases 81 94 162 33
*Adjusted for age (5-year categories), smoking (never, former, current: 1-14, 15-24, $25 cigarettes per day), alcohol
(7 categories in men, 5 categories in women), family history of myocardial infarction (age ,60 y in men and age ,65
y in women), body mass index (quintiles), vitamin supplement use, vitamin E use, physical activity, aspirin use, 7 time
periods for women, 4 time periods for men, hypertension and hypercholesterolemia, total energy intake, and among
women, postmenopausal hormone use.
FRUIT AND VEGETABLE INTAKE AND ISCHEMIC STROKE
1238 JAMA, October 6, 1999—Vol 282, No. 13 ©1999 American Medical Association. All rights reserved.
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vegetables foods in themselves. Slightly
stronger protective associations were
seen in the nonusers of supplements,
suggesting that constituents of multi-
vitamins may contribute to the appar-
ent protective effect of fruits and veg-
etables. There was no clear modification
of the relation of fruit and vegetable con-
sumption to risk of ischemic stroke by
smoking, but current smokers may gain
a slightly greater benefit from eating
more fruits and vegetables than never or
past smokers.
These data support a protective ef-
fect of higher consumption of fruits and
vegetables—in particular cruciferous
and green leafy vegetables, citrus fruits,
and citrus juice—against risk of ische-
mic stroke. Our results provide fur-
ther support for the recommendation
to consume at least 5 servings of fruits
and vegetables a day.
Funding/Support: This research was supported by
grants HL34595, HL35464, CA40356, CA55075, and
DE12102 from the Office of Dietary Supplements, Na-
tional Institutes of Health, Bethesda, Md, and by the
State of Florida Department of Citrus, Lake Alfred.
Acknowledgment: We are indebted to the partici-
pants of the Health Professionals’ Follow-up Study and
the Nurses’ Health Study for their continued coop-
eration and participation; to Al Wing, MBA, Mira Kauf-
man, Karen Corsano, and Marcia Goetsch for com-
puter assistance; to Jill Arnold, Betsy Frost-Hawes, Kerry
Demers, Mitzi Wolff, Gary Chase, and Barbara Egan
for their assistance in the compilation of data; and to
Laura Sampson, RD, for maintaining our food com-
position tables.
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