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Nutritional Epidemiology
Low Intake of Fruits, Berries and Vegetables Is Associated with Excess
Mortality in Men: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD)
Study1
Tiina H. Rissanen,*† Sari Voutilainen,* Jyrki K. Virtanen,* Birgitta Venho,* Meri Vanharanta,*
Jaakko Mursu* and Jukka T. Salonen *†**2
*Research Institute of Public Health, University of Kuopio, Kuopio, Finland; †Department of Public Health
and General Practice, University of Kuopio, Kuopio, Finland; and **The Inner Savo Health Center,
Suonenjoki, Finland
KEY WORDS:
●
vegetables
●
fruits
●
prospective study
●
mortality risk
●
cardiovascular disease
findings support a protective role for fruits and vegetables in
CVD, although the results were inconsistent. Only a few
previous cohort studies have been conducted in which an
association between intake of fruits and vegetables and overall
mortality was observed (3– 6).
There are major differences in the prevalence of CVD
among populations. In the Seven Countries Study (7), the
lowest 25-y CHD-related mortality rates were found in Southern European countries and in Japan compared with countries
with high mortality rates such as the United States, the
Netherlands and Finland. In the Eastern part of Finland, the
mortality rate was 10 times higher than in Crete in which the
Mediterranean diet rich in plant foods and low in animal foods
is consumed. We wanted to test the hypothesis that a diet
resembling the Mediterranean diet, i.e., high in fruit, berry and
vegetable intake, is associated with a decreased risk of allcause, CVD- and non-CVD-related mortality in a prospective
cohort study of middle-aged Finnish men.
Despite the decline in age-adjusted mortality from coronary
heart disease (CHD)3 during the past 30 y, CHD is still the
most common cause of death in Finland and many other
industrialized countries (1). Intake of fruits, berries and vegetables may reduce cardiovascular disease (CVD) risk through
the beneficial combination of antioxidants, fiber, potassium,
magnesium and other phytochemicals. Because dietary recommendations concern the intake of whole foods rather than
nutrients, the effects of these constituents might be best evaluated by investigating the intake of fruits and vegetables.
Furthermore, confirmation of the associations between foods
and disease risk will improve the recommendations made for
heart healthy diets. Ness and Powles (2) reviewed findings
from studies that focused directly on fruit and vegetable intake
rather than on nutrient intakes in association with CVD. The
1
Supported by Finnish Cultural Foundation (T.H.R.) and Academy of Finland
(grants 41471, 1041086 and 2041022 J.T.S.)
2
To whom correspondence and reprint request should be addressed.
E-mail: [email protected].
3
Abbreviations used: BMI, body mass index; CHD, coronary heart disease;
CI, confidence interval; CVD, cardiovascular disease; ICD-9, International Classification of Diseases, 9th ed.; KIHD, Kuopio Ischaemic Heart Disease Risk Factor
Study; RR, relative risk.
SUBJECTS AND METHODS
Study population. Subjects were participants of the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study (8). This study was
designed to investigate risk factors for CVD, atherosclerosis and
0022-3166/03 $3.00 © 2003 American Society for Nutritional Sciences.
Manuscript received 19 July 2002. Initial review completed 16 August 2002. Revision accepted 2 October 2002.
199
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ABSTRACT Diets rich in fruits and vegetables have been of interest because of their potential health benefits
against chronic diseases such as cardiovascular disease (CVD) and cancer. The aim of this work was to assess the
association of the dietary intake of a food group that includes fruits, berries and vegetables with all-cause,
CVD-related and non-CVD-related mortality. The subjects were Finnish men aged 42– 60 y examined in 1984 –1989
in the prospective Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. Dietary intakes were assessed by 4-d
food intake record during the baseline phase of the KIHD Study. The risk of all-cause and non-CVD-related deaths
was studied in 2641 men and the risk of CVD-related death in 1950 men who had no history of CVD at baseline.
During a mean follow-up time of 12.8 y, cardiovascular as well as noncardiovascular and all-cause mortality were
lower among men with the highest consumption of fruits, berries and vegetables. After adjustment for the major
CVD risk factors, the relative risk for men in the highest fifth of fruit, berry and vegetable intake for all-cause death,
CVD-related and non-CVD-related death was 0.66 [95% confidence interval (CI) 0.50 – 0.88], 0.59 (0.33–1.06), and
0.68 (0.46 –1.00), respectively, compared with men in the lowest fifth. These data show that a high fruit, berry and
vegetable intake is associated with reduced risk of mortality in middle-aged Finnish men. Consequently, the
findings of this work indicate that diets that are rich in plant-derived foods can promote longevity. J. Nutr. 133:
199 –204, 2003.
200
RISSANEN ET AL.
related outcomes in a population-based, randomly selected sample of
men from eastern Finland (8). The baseline examinations were carried out between March 1984 and December 1989. The study sample
was composed of 3235 men aged 42, 48, 54 or 60 y at baseline
examination. Of these, 2682 (82.9%) participated. The baseline
characteristics of the entire study population were described previously (8). The study protocol was approved by the Research Ethics
Committee of the University of Kuopio. All subjects gave written
informed consent.
When analyzing CVD-related mortality, subjects with a history of
CVD were excluded because these conditions might have affected
their dietary choices. After exclusions, complete data were available
for 1950 men (115 events). Risk of all-cause and non-CVD-related
mortality was estimated without exclusions; thus the analyses included 2641 men (485 and 245 events, respectively).
Assessment of nutrient intake. The consumption of foods was
assessed at the time of blood sampling during the baseline phase of
the KIHD study. Subjects were instructed on the use of household
measures for quantitative recording of their food intake during the 4 d
of data collection. A nutritionist gave the instructions and checked
the completed food intake records. Dietary intake of nutrients and
foods was calculated using NUTRICA software (version 2.5; National Public Health Institute, Turku, Finland). The software is
compiled using mainly Finnish values of nutrient composition of
foods, and takes into account losses of vitamins in food preparation.
The nutrient compositions of foods in NUTRICA software version
2.5 were analyzed mainly in the 1990s, reflecting the latest data on
vitamin contents of fruits and vegetables. For the assessment of
dietary fatty acids, an earlier version (1.0) was used because of the
changes in fatty acid contents of margarines in Finland during last
15 y. In total, the database contains comprehensive data for 1300
food items and dishes and 30 nutrients.
In this study, the intake of fruits, berries and vegetables also
included jams, nectars and juices but did not include potatoes. All
nutrients were adjusted for dietary energy intake by using the residual
method (9,10). Energy adjustment is based on the idea that a larger,
more physically active person requires a higher energy intake, which
is associated with a higher absolute intake of all nutrients. Therefore
energy adjustment takes into account differences in energy requirements among individuals. The residuals were standardized by the
mean nutrient intake of a subject consuming 10 MJ/d, the approximate mean total energy intake in the present study population.
Other measurements. Assessments of medical history and medications, family history of diseases, smoking, alcohol consumption and
blood pressure were performed as described previously (11). Subjects
with systolic blood pressure ⱖ160 mm Hg or diastolic blood pressure
ⱖ95 mm Hg or who used antihypertensive drugs were classified as
hypertensive. The collection of blood specimens (11) and the measurement of maximal oxygen uptake (12), serum lipids (13), lipoproteins (14) and 24-h urinary excretion of nicotine metabolites (15)
have been described. Diabetes was defined as either a previous diagnosis of diabetes with dietary, oral or insulin treatment, or fasting
whole blood glucose concentration ⱖ6.7 mmol/L. Serum insulin was
measured with a Novo Biolab RIA (Novo Nordisk, Bagsvaerd, Denmark). Plasma fibrinogen was determined with a coagulation method
from Dade AG (Dudingen, Switzerland) by a coagulometer (KC 4,
Heinrich Amelung, Lemgo, Germany) and serum haptoglobin by
immunoturbidimetric method (Dade Behringin, Marbug, Germany).
Follow-up events. Deaths were ascertained by a computer linkage
to the national death registry using the Finnish social security number. There were no losses to follow-up. All deaths that occurred from
the study entry to December 31, 2000, were included. Deaths were
coded according to the International Classification of Diseases (9th
ed.; ICD-9) (16). All deaths and deaths caused by CVD (ICD-9 codes
390 – 459) were chosen as end points. The mean follow-up time to
death was 12.8 y (range 0 –16.8 y), which equals ⬃33,800 personyears of observation. In the present sample, there were 485 all-cause
deaths, of which 245 resulted from CVD-related causes and 240 from
non-CVD-related causes.
Statistical analysis. Data were analyzed using SPSS 10.0 for
Windows (Chicago, IL). Subjects were divided into fifths according
to their mean intake of fruits, berries and vegetables. The values in
the lowest fifth were used as the reference category. The mean of each
fifth was reported and compared by ANOVA for the baseline characteristics of 2641 cohort members. The relationships of dietary
intake of fruits, berries and vegetables with the risk of mortality and
survival were analyzed with the Cox ‘proportional hazards’ model.
Five different sets of covariates were used: 1) age and examination
years; 2) age, examination years, smoking (measured as urinary excretion of nicotine metabolites) and alcohol consumption; 3) model
2 and systolic and diastolic blood pressure, body mass index (BMI),
diabetes, serum HDL and LDL cholesterol and triglyceride levels; 4)
model 3 and maximal oxygen uptake in an exercise test; 5) model 4
and energy adjusted intakes of vitamin C and E, ␤-carotene, lycopene, fiber and folate. Relative hazards (risks), adjusted for covariates,
were estimated as antilogarithms of coefficients in multivariate models. Their confidence intervals (CI) were estimated under the assumption of asymptotic normality of the estimates. The correlations between cardiovascular risk factors and dietary intake of fruits, berries
and vegetables were estimated by Pearson’s correlation coefficients.
All tests of significance were two-sided and a P-value of ⬍ 0.05 was
considered significant.
RESULTS
The daily intake of fruits, berries and vegetables was 284
⫾ 182 g (mean ⫾ SD). The subjects were divided into fifths of
the mean daily intake (⬍133, 133–214, 215–293, 294 – 408
and ⬎408 g/d), and the main characteristics of the subjects in
those categories are shown in Table 1. Men in the highest fifth
of intake were younger, smoked less and drank less alcohol. In
addition, blood pressure, plasma levels of fibrinogen, total and
LDL cholesterol were lower among these men compared with
the others. In addition, the men in the highest intake fifth of
fruits, berries and vegetables consumption had a higher intake
of dietary fiber, vitamin C and E, folate, ␤-carotene and total
energy than others.
During a mean follow-up time of 12.8 y, the occurrences of
CVD death, non-CVD death as well as total mortality were
the highest among men with the lowest consumption of fruits,
berries and vegetables (Table 1). The intake of fruits, berries
and vegetables was 41% lower in men who died of CVD during
the first 5 y of follow-up and 20% lower with the inclusion of
all CVD-deaths during the whole follow-up time of 12.8 y
compared with the men who survived. The respective estimates concerning non-CVD-related and all-cause deaths were
21 vs. 12% and 13 vs. 16%, (P ⬍ 0.01 for all differences).
In a Cox ‘proportional hazards’ model, we observed a significant inverse association between the intake of fruits, berries and vegetables and all-cause, CVD- and non-CVD-related
mortality (Table 2). In model 1, after adjustment for age and
examination years, men in the highest intake fifth had a
relative risk (RR) of overall death of 0.65 (95% CI 0.49 –
0.86), CVD-related death of 0.43 (95% CI 0.24 – 0.76) and
non-CVD-related death of 0.56 (95% CI 0.38 – 0.83) compared with men in the lowest intake fifth. An additional
adjustment for traditional CHD risk factors (models 2 and 3)
did not notably affect the results (Table 2). However, in model
5 (adjustment for model 3 ⫹ maximal oxygen uptake and
dietary factors: intakes of vitamin C and E, ␤-carotene, lycopene, folate and fiber), an inverse trend was observed only
when the risk of all-cause death was analyzed. The cumulative
increase of all-cause (Fig. 1B) and CVD-related mortality
(adjusted for age and examination years) (Fig. 1A) in fifths of
fruit, berry and vegetable intake is presented to illustrate the
earlier occurrence of deaths among men in the two lowest
fifths compared with the others.
We also studied the protective effect of dietary intake of
vitamin C and E, ␤-carotene, lycopene, folate and fiber against
mortality (adjusted for age, examination years, smoking, uri-
FRUITS, BERRIES AND VEGETABLES AND MORTALITY
201
TABLE 1
Baseline characteristics of the 2641 study participants in the fifths of intake of fruits, berries and vegetables
in the Kuopio Ischaemic Heart Disease Risk Factor Study1
⬍133
Fruit, berry and vegetable intake, g/d
Characteristic
Group (fifth)
Men at risk, n
Events, n
All death (485)2
CVD (115)3
Non-CVD (245)2
Fruit, berry and vegetable intake,4 g/d
Biochemical variables and other risk
factors
Age, y
Body mass index, kg/m2
Systolic blood pressure, mmHg
Diastolic blood pressure, mmHg
Plasma fibrinogen, g/L
Serum insulin, pmol/L
Blood glucose, mmol/L
Serum total cholesterol, mmol/L
Serum LDL cholesterol, mmol/L
Serum HDL cholesterol, mmol/L
Serum triglycerides, mmol/L
Urinary nicotine metabolites, mg/d
Serum haptoglobin, g/L
Dietary factors
Energy, MJ/d
Alcohol, g/wk
Cholesterol, mg/d
Saturated fat, E%/d
Fiber, g/d
Vitamin E, mg/d
Vitamin C, mg/d
Folate, ␮g/d
␤-carotene, mg/d
Percentage of total
Smokers
Hypertension
Family history of ischaemic heart disease
Diabetes
Body mass index ⱖ30, kg/m2
1
2
3
4
82
1
529
2
528
145
39
72
⫾ 34
111
25
55
⫾ 23
53.7 ⫾
27.0 ⫾
135.6 ⫾
89.3 ⫾
3.11 ⫾
82.6 ⫾
4.9 ⫾
6.02 ⫾
4.14 ⫾
1.33 ⫾
1.3 ⫾
8.6 ⫾
1.6 ⫾
9.2
93
393
20.3
20.6
7.4
32.8
200
1.1
133–214
174
215–293
3
528
252
87
14
43
⫾ 22
⬎408
294–408
4
528
347
68
20
36
⫾ 33
P for
heterogeneity
5
528
562
74
17
34
⫾ 167
5.0 53.1 ⫾ 5.0 53.0 ⫾ 5.1 53.0 ⫾ 5.1 52.6 ⫾ 5.4
4.0 27.1 ⫾ 3.5 26.5 ⫾ 3.4 27.0 ⫾ 3.7 26.7 ⫾ 3.3
18.0 134.9 ⫾ 16.9 133.4 ⫾ 17.1 134.0 ⫾ 16.8 132.8 ⫾ 16.2
10.8 88.9 ⫾ 10.6 88.6 ⫾ 10.5 89.3 ⫾ 10.3 87.5 ⫾ 10.2
0.50 3.06 ⫾ 0.57 3.02 ⫾ 0.53 2.92 ⫾ 0.51 2.98 ⫾ 0.57
54.3 89.6 ⫾ 49.4 78.2 ⫾ 43.0 81.7 ⫾ 50.4 79.2 ⫾ 51.7
1.6
4.8 ⫾ 1.1
4.7 ⫾ 1.0
4.7 ⫾ 0.9
4.8 ⫾ 1.3
1.09 5.99 ⫾ 1.13 5.88 ⫾ 1.03 5.89 ⫾ 1.03 5.76 ⫾ 1.04
1.04 4.08 ⫾ 1.05 4.02 ⫾ 0.99 4.04 ⫾ 0.97 3.92 ⫾ 0.98
0.33 1.29 ⫾ 0.28 1.30 ⫾ 0.29 1.26 ⫾ 0.28 1.28 ⫾ 0.30
0.7
1.3 ⫾ 0.8
1.3 ⫾ 0.9
1.4 ⫾ 0.9
1.3 ⫾ 0.7
10.0
6.4 ⫾ 7.8
5.8 ⫾ 8.8
4.9 ⫾ 7.3
4.4 ⫾ 6.8
0.7
1.4 ⫾ 0.6
1.3 ⫾ 0.5
1.2 ⫾ 0.5
1.3 ⫾ 0.5
⬍0.001
⬍0.001
⬍0.001
0.010
0.037
0.055
0.023
⬍0.001
0.293
0.339
0.001
0.006
0.004
0.613
⬍0.001
⬍0.001
⫾ 2.5
9.9
⫾ 136
82
⫾ 155
401
⫾ 4.7 18.8
⫾ 8.3 24.2
⫾ 2.8
8.5
⫾ 18.7 49.9
⫾ 58
236
⫾ 0.9
1.8
⫾ 2.8 10.0
⫾ 149
74
⫾ 158
403
⫾ 4.3 18.3
⫾ 8.0 24.9
⫾ 2.7
8.8
⫾ 32.5 65.0
⫾ 67
250
⫾ 1.3
2.2
⫾ 2.6 10.0
⫾ 170
61
⫾ 152
384
⫾ 3.9 16.8
⫾ 7.6 26.5
⫾ 2.6
9.6
⫾ 28.8 83.9
⫾ 59
268
⫾ 1.8
2.7
⫾ 2.4 10.2
⫾ 108
64
⫾ 137
386
⫾ 3.8 15.8
⫾ 7.7 29.4
⫾ 2.9 10.4
⫾ 34.9 129.2
⫾ 62
315
⫾ 2.1
4.1
⫾ 2.6
⫾ 97
⫾ 156
⫾ 3.6
⫾ 9.8
⫾ 3.2
⫾ 63.3
⫾ 81
⫾ 3.9
⬍0.001
0.001
0.131
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
⬍0.001
51
46
50
5.9
18
36
48
51
6.1
18
31
46
46
5.3
15
21
52
50
3.8
19
19
48
49
6.1
15
⬍0.001
0.803
0.666
0.433
0.282
Values are means ⫾ SD, n or %.
Counted from 2641 men.
Counted from 1950 men free of CVD at study baseline.
Four-day mean.
nary excretion of nicotine metabolites, alcohol consumption,
systolic and diastolic blood pressure, BMI, diabetes, serum
HDL and LDL cholesterol and triglyceride levels). Nutrients
that were negatively associated with all-cause mortality were
vitamin C (explaining 10.4% of protection of fruits, berries
and vegetables), folate (6.5%), lycopene (5.6%) and vitamin E
(5.3%). Corresponding nutrients for CVD mortality were vitamin C (19.4%), folate (14.6%) and vitamin E (1.9%) and
for non-CVD mortality, vitamin C (57.9%), lycopene (22.6%)
and vitamin E (14.6%).
To study the possible mechanisms behind these associations, we screened the correlations between the intake of
fruits, berries and vegetables and common cardiovascular risk
factors (Table 3). The strongest negative correlations were
observed between the intake of fruits, berries and vegetables
and serum haptoglobin (r ⫽ ⫺0.16) and plasma fibrinogen (r
⫽ ⫺0.10). Weaker negative correlations were also found between the intake of fruits, berries and vegetables and age,
serum total, HDL and LDL cholesterol and also diastolic and
systolic blood pressures. We also found a positive correlation
between the maximal oxygen uptake and intake of fruits,
berries and vegetables (r ⫽ 0.11).
DISCUSSION
This prospective cohort study in middle-aged men from
eastern Finland indicates that a high consumption of fruits,
berries and vegetables is associated with a reduced risk of
CVD-related, non-CVD related and overall mortality. Although it is possible that this finding can be explained in part
by the healthy lifestyles that are related to a high fruit, berry
and vegetable intake, adjustment for traditional CVD risk
factors or lifestyle habits cannot fully account for the observed
beneficial effect of higher consumption.
Although several prospective studies have directly related
fruit and vegetable intake to CVD (2,17), few studies have
reported an association between fruits and vegetables and
overall mortality (3– 6). In The Nutrition Status Survey in
RISSANEN ET AL.
202
TABLE 2
Relative risks of all-cause death, cardiovascular disease (CVD)-related and non-CVD-related death in the fifths of intake of fruits,
berries and vegetables in the Kuopio Ischaemic Heart Disease Risk Factor Study
Fruit, berry and vegetable intake, g/d
Group
Incidence of all-cause death, n
Model 12
Model 23
Model 34
Model 45
Model 56
Incidence of cardiovascular death, n
Model 12
Model 23
Model 34
Model 45
Model 56
Incidence of noncardiovascular death, n
Model 12
Model 23
Model 34
Model 45
Model 56
1
2
3
4
5
6
⬍133
133–214
215–293
294–408
⬎408
1
529
1
1
1
1
1
360
1
1
1
1
1
528
1
1
1
1
1
2
528
0.86 (0.67–1.10)
0.86 (0.67–1.10)
0.86 (0.67–1.11)
0.90 (0.70–1.15)
0.90 (0.69–1.16)
388
0.64 (0.39–1.06)
0.71 (0.42–1.17)
0.77 (0.46–1.30)
0.76 (0.45–1.30)
0.76 (0.44–1.30)
528
0.77 (0.55–1.10)
0.85 (0.69–1.21)
0.85 (0.59–1.20)
0.88 (0.62–1.26)
0.90 (0.63–1.30)
3
528
0.70 (0.54–0.92)
0.70 (0.54–0.92)
0.73 (0.56–0.96)
0.80 (0.61–1.05)
0.80 (0.60–1.07)
393
0.35 (0.19–0.64)
0.42 (0.23–0.79)
0.46 (0.25–0.87)
0.49 (0.26–0.91)
0.50 (0.26–0.96)
528
0.60 (0.41–0.87)
0.70 (0.48–1.02)
0.70 (0.47–1.01)
0.75 (0.51–1.10)
0.79 (0.53–1.19)
4
528
0.56 (0.42–0.75)
0.56 (0.42–0.75)
0.57 (0.43–0.77)
0.62 (0.46–0.83)
0.63 (0.45–0.88)
407
0.48 (0.28–0.82)
0.59 (0.34–1.02)
0.56 (0.33–0.97)
0.60 (0.34–1.03)
0.62 (0.33–1.16)
528
0.43 (0.28–0.65)
0.52 (0.34–0.79)
0.52 (0.34–0.79)
0.56 (0.37–0.86)
0.63 (0.39–1.02)
5
528
0.65 (0.49–0.86)
0.65 (0.49–0.86)
0.66 (0.50–0.88)
0.74 (0.55–0.98)
0.76 (0.50–1.16)
433
0.43 (0.24–0.76)
0.56 (0.31–1.00)
0.59 (0.33–1.06)
0.61 (0.34–1.10)
0.66 (0.28–1.55)
529
0.56 (0.38–0.83)
0.69 (0.46–1.02)
0.68 (0.46–1.00)
0.74 (0.50–1.10)
0.87 (0.49–1.60)
P1
P for
trend
0.003
0.003
0.005
0.036
0.201
⬍0.001
⬍0.001
⬍0.001
0.002
0.021
0.004
0.050
0.078
0.101
0.342
0.001
0.020
0.020
0.037
0.127
0.004
0.062
0.052
0.135
0.688
⬍0.001
0.005
0.004
0.019
0.184
Highest vs. lowest fifth.
Adjusted for age and examination years.
Adjusted for model 1 and urinary excretion of nicotine metabolites and alcohol consumption.
Adjusted for model 2 and body mass index, systolic and diastolic blood pressure, diabetes, serum LDL, HDL and triglycerides.
Adjusted for model 3 and maximal oxygen uptake.
Adjusted for model 4 and dietary factors: energy adjusted (by residual method) intakes of vitamin C and E, ␤-carotene, lycopene, folate and fiber.
Massachusetts (3), the authors followed 725 elderly men and
women for 9 –12 y, and reported that intake of vegetables but
not fruits was significantly associated with reduced risk of
overall and cardiovascular mortality. In The Study of Men
Born in 1913 (5), it was concluded that at the 16-y follow-up
cardiovascular as well as total mortality was significantly lower
among men with high fruit consumption. In The Finnish
Mobile Clinic Study, there was an inverse association between
the intake of fruits and vegetables and coronary mortality,
which was particularly clear among men (18). The authors
reported that especially among women, the beneficial effect of
high intake of vegetables was weakened after adjustment for
vitamin E and C and carotenoids. However, in men, this
adjustment did not appreciably alter the beneficial effect,
which suggests that vegetables may contain favorable constituents other than vitamins. A recently published study from
the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study with 9600 participants and
160,000 person-years of follow-up showed an inverse association of fruit and vegetable intake with the CVD risk and
all-cause mortality in the general U.S. population (6). Our
results provide further evidence for the hypothesis that a high
intake of fruits, berries and vegetables is associated with reduced risk of mortality.
In The Finnish Mobile Clinic Study and in The Seven
Countries Study among middle-aged Finnish men, the daily
intake of fruits, berries and vegetables was quite low (160 –200
g/d) (4,18). In the Nutrition Status Survey in Massachusetts
middle-aged men consumed ⬃510 g/d of fruits and vegetables
(3). In the Health Professionals’ Follow-Up Study, and in
Nurses’ Health Study (19) and in the Framingham Heart
Study (20), the intake of fruits and vegetables was ⬃5 servings/d and in the Women’s Health Study (17) 6 servings/d. An
example of the standard portion size is one banana or a small
glass of juice. In the Framingham Heart Study, potatoes were
also included in the total amount of fruits and vegetables,
which was not done in the other studies. In Finland the intake
of potatoes is accompanied by a high intake of animal and
dairy products (7), and in our study population, there was a
positive correlation between the intake of potatoes and the
intake of butter, meat products and saturated fatty acids (data
not shown). Among the guidelines for the prevention of CVD,
there is a recommendation to consume at least 400 g/d of fruits
and vegetables (21). Thus, on the basis of our study and the
other studies done on Finnish subjects (4,18), their consumption of fruits and vegetables falls somewhat short of the recommendations.
In the above-mentioned studies, the food intake was estimated using a dietary history method (4,18), food-frequency
questionnaire (17,19) or a single 24-h recall (20). In our study,
the dietary information we used was a 4-d food record, which
is more convenient to use than a food-frequency questionnaire. The 4-d food record was used in only one of the studies
cited (3). A major advantage of a food record compared with
recalls is that it does not rely on memory. Another strength is
that portion sizes can be measured directly rather than estimated afterward (22). This method also has some disadvantages, i.e., it does not take into account the effect of season,
and study participants can make changes to their diet to make
the record look better.
There are likely to be multiple mechanisms through which
fruits, berries and vegetables could protect against CHD. The
proposed beneficial substances include antioxidant vitamins,
folate, fiber, potassium and magnesium. Antioxidant compounds and polyphenols in fruits and vegetables, such as
vitamin C, carotenoids and flavonoids may have a modest
effect on the risk of CHD by preventing the oxidation of
cholesterol and other lipids in the arteries. We showed, for
FRUITS, BERRIES AND VEGETABLES AND MORTALITY
example, in the KIHD study that low plasma vitamin C
concentrations are associated with an increased risk of acute
coronary events in men (14). We also showed that in men, low
circulating lycopene concentration is associated with early
atherosclerosis (23,24) and with excess incidence of acute
coronary events and stroke (25). However, results of epidemiologic studies concerning antioxidant vitamins and flavonoids
and risk of CHD are inconsistent (26,27). Folate, found especially in green leafy vegetables, helps to lower blood homocysteine, a proposed risk factor for CVD (28). We reported
earlier in the KIHD study that men with low dietary intake of
folate (9) or low serum levels of folate (29) have an increased
risk of acute coronary events. Fruits and vegetables are rich in
soluble fiber, and in many epidemiologic studies, dietary fiber
has been shown to be associated with a decreased risk of CVD
(30). The main cardioprotective properties of fiber could be
explained by the hypocholesterolemic effects, which result
mainly from alterations in the hepatic cholesterol and lipoprotein metabolism (30). There are probably several other potential components in fruits, berries and vegetables that may have
protective effects against CVD. There is increasing evidence
from epidemiologic and clinical studies that potassium and
magnesium intakes have an important role in regulating blood
pressure (31–33). High potassium and magnesium intakes may
also have other beneficial effects independent of their influence on blood pressure, such as reducing the risk of stroke.
FIGURE 1 Cumulative cardiovascular disease (CVD)-related
(panel A) and all-cause (panel B) mortality up to 15 y and 9 mo of
follow-up according to the fifths of intake of fruits, berries and vegetables in middle-aged Finnish men.
203
TABLE 3
Pearson’s correlation coefficients (r) and statistical
significance of the associations between the intake of fruits,
berries and vegetables and common cardiovascular risk
factors in middle-aged eastern Finnish men in the Kuopio
Ischaemic Heart Disease Risk Factor Study
Age, y
Systolic blood pressure, mmHg
Diastolic blood pressure, mmHg
Plasma fibrinogen, g/L
Serum insulin, pmol/L
Blood glucose, mmol/L
Serum total cholesterol, mmol/L
Serum LDL cholesterol, mmol/L
Serum HDL cholesterol, mmol/L
Urinary nicotine metabolites, mg/d
Serum haptoglobin, g/L (n ⫽ 690)
Maximal oxygen uptake, mL/(kg 䡠 min)
r
P
⫺0.07
⫺0.05
⫺0.05
⫺0.10
⫺0.03
⫺0.01
⫺0.07
⫺0.06
⫺0.06
⫺0.15
⫺0.16
0.11
⬍0.001
0.006
0.017
⬍0.001
0.149
0.569
⬍0.001
0.004
0.003
⬍0.001
⬍0.001
⬍0.001
Last, it cannot be excluded that simply the low contents of fat,
energy and sodium in most vegetables and fruits may reduce in
part the risk of obesity and high blood pressure and hence
CHD and CVD mortality. In our present study, the intake of
fruits, berries and vegetables correlated negatively with serum
haptoglobin, which is an inflammation-inducible plasma protein and a marker of inflammation. The protective effect of a
high intake of fruits, berries and vegetables may be explained
in part by the decreased blood haptoglobin levels. Although
the correlations between serum haptoglobin and all-cause,
CVD-related and non-CVD-related mortality were also positive, the correlations were very low and may not have any
clinical importance.
In the present study, the adjustment for nutritional factors
(intake of energy adjusted vitamin C and E, ␤-carotene, lycopene, folate and fiber) attenuated the protective effect of
intake of fruits, berries and vegetables against mortality; thus,
these may be the main protective nutrients in these foods.
Intake of energy-adjusted folate, lycopene, vitamin C and E
explained 28% of the protective effect of fruits, berries and
vegetables against all-cause mortality, and intake of vitamin C,
folate and vitamin E explained 36% of the protective effect
against adjusted CVD mortality. We also found that maximal
oxygen uptake in the exercise test correlated strongly with
intakes of fruits, berries and vegetables. Men who consumed
more plant products seemed to have healthier lifestyles than
men who consumed fewer of these foods. Therefore, when
studying associations between nutrients and diseases, it is
important to include not only the traditional risk factors in the
statistical models, but also other factors that are a part of a
healthy lifestyle, such as exercise.
In conclusion, the findings of this prospective cohort study
indicate that a higher intake of fruits, berries and vegetables is
associated with a reduced risk of CVD-related, non-CVD
related and overall mortality in middle-aged men in eastern
Finland. Our findings provide additional evidence that higher
intakes of fruit and vegetable can prevent heart diseases and
mortality.
ACKNOWLEDGMENTS
We thank the personnel of the Research Institute of Public
Health and Oy Jurilab Ltd. (www.jurilab.com) for helping with data
collection.
RISSANEN ET AL.
204
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