Original Research
Vitamin C Intake and Risk of Ischemic Heart Disease in
a Population with a High Prevalence of Smoking
Chung Mo Nam, PhD, Kyung Won Oh, PhD, Kang Hee Lee, MD, PhD, Sun Ha Jee, PhD, Seung Yun Cho, MD, PhD,
Won Heum Shim, MD, PhD, Il Suh, MD, PhD
Department of Preventive Medicine and Public Health (C.M.N., K.H.L., I.S.), Department of Internal Medicine (S.Y.C., W.H.S.),
Yonsei University College of Medicine, Department of Public Health, Graduate School of Yonsei University (K.W.O.),
Department of Epidemiology and Health Promotion, Graduate School of Health Science and Management (S.H.J.), Yonsei
University, Seoul, KOREA
Key words: vitamin C intake, Ischemic heart disease, case-control study, Republic of Korea
Objective: Epidemiological data on the relationship between vitamin C intake and ischemic heart disease
(IHD) risk are limited in the Asian population, with a high prevalence of smoking. This study aims to investigate
the association between vitamin C intake and the incidence of non-fatal IHD in Korean men.
Methods: The case group consisted of 108 patients with electrocardiogram-confirmed myocardial infarction
or angiographically confirmed (!50% stenosis) coronary artery disease (CAD) who were admitted to a
university teaching hospital in Seoul, Korea. The controls were 142 age-matched patients admitted to the
departments of ophthalmology and orthopedic surgery at the same hospital. Vitamin C intake was assessed by
a nutritionist using a semi-quantitative food frequency method, and body mass index (BMI), tobacco use and past
history of cardiovascular disease were determined by examination and interview.
Results: After controlling for cardiovascular risk factors, including BMI, smoking, past history of hypertension, past history of hyperlipidemia, dietary intakes of energy, total fat (or subtype of fat), cholesterol,
"-carotene, and vitamin E, the odds ratio (OR) of non-fatal IHD was 0.34 (95% confidence interval (CI)
0.13– 0.90) in the highest tertile of vitamin C intake compared with those in the lowest tertile. In a subgroup
analysis, which compared nonsmokers in the highest tertile of vitamin C intake to current smokers in the lowest
tertile of vitamin C intake, the odds ratio of developing non-fatal IHD was 0.12 (95% CI 0.02– 0.77).
Conclusion: This study suggests that higher intake of vitamin C is associated with the decreased risk of
non-fatal IHD in a population with a high prevalence of smoking.
INTRODUCTION
In Korea, cardiovascular disease (CVD) has emerged as the
leading cause of death. Even though mortality due to IHD is
relatively low compared to that of Western countries, its rate
rapidly increased between 1984 and 1993, stabilizing thereafter. In 1999, the age-adjusted death rates for men and women
were 11.9 and 7.5 per 100,000. These rates were 3.8 and 3.6
times higher than the rates in 1984 for men and women,
respectively [4]. Average daily vitamin C intake, estimated
from 24-hour recall, of Koreans was 76.2 mg in 1988 and
increased to 123.1 mg in 1998 [5]. Although, average vitamin
C intake was higher than the Korean recommended dietary
allowance (RDA) (70 mg/day for healthy, nonsmoking adults),
18.1% consume less than 75% of the RDA [6].
The concept of the relationship between diet and ischemic
heart disease (IHD) has changed considerably over the past two
decades because of critical breakthroughs in our understanding
of the mechanisms of the disease. Biochemical, clinical and
epidemiologic evidence suggests that oxidants are involved in
the development and clinical expression of coronary heart
disease and that these antioxidants may contribute to lowering
the disease risk [1–3]. One such antioxidant nutrient of considerable interest is vitamin C. Carr et al. [1] reported a significant inverse association between vitamin C intake and cardiovascular disease risk in 7 of 12 prospective cohort studies.
Address reprint requests to: Il Suh, MD, PhD, Department of Preventive Medicine and Public Health, Yonsei University College of Medicine 134 Shinchon-dong
Seodaemun-gu 120-752 Seoul, Republic of Korea. E-mail: [email protected].
Journal of the American College of Nutrition, Vol. 22, No. 5, 372–378 (2003)
Published by the American College of Nutrition
372
Vitamin C Intake and Ischemic Heart Disease
Cigarette smoking is an important risk factor for IHD and
has also been shown in Koreans [7, 8]. Korean men have the
highest prevalence of smoking in the world. Although the
prevalence of smoking among Korean men was 64.9% in 1998
and has since declined, it still remains very high [4]. A significant amount of research indicates that smokers have a higher
requirement for vitamin C than nonsmokers [1, 2]. Smokers
show significantly higher intakes of energy, total fat and saturated fatty acid, and lower intakes of vitamin C, vitamin E,
"-carotene and polyunsaturated fat than nonsmokers. In addition to dietary intake, smokers have lower plasma vitamin C
levels than nonsmokers, because smoking increases the turnover of and decreases the absorption of vitamin C. Some of
these differences may further exacerbate the deleterious effects
of cigarette smoking on coronary heart disease [9].
However, little information is available on the relationship
between vitamin C intake and the incidence of IHD in population with a high prevalence of smoking. In this study, we
investigated the association between vitamin C intake and the
incidence of IHD in Korean men. This is of particular concern
given the growing incidence of IHD in this area of the world.
MATERIALS AND METHODS
Subjects
Cases and controls were selected from the Cardiovascular
Center at a university teaching hospital in Seoul admitted
during the period October, 1995 to July, 1996. The cases were
108 male patients with a first acute myocardial infarction (MI)
(50 patients) or new diagnosis of angina pectoris (58 patients).
The inclusion criteria for the cases were (1) younger than 75
years of age, (2) onset of symptoms developed within a month
of admission, (3) acute MI confirmed by electrocardiogram
(ECG) of cardiac enzyme measurement, (4) angina pectoris
confirmed by coronary angiogram (50% or more occlusion in at
least one of three main coronary arteries). One hundred and
forty two controls, matched by age within 10 years, were
selected from male patients admitted to the department of
ophthalmology (69 patients) and orthopedic surgery (73 patients). The inclusion criteria for the controls were (1) younger
than 75 years of age, (2) confirmed normal ECG’s when were
admitted to hospital, (3) no past history of myocardial infarction or angina pectoris.
Methods
A trained interviewer interviewed cases and controls in the
hospital. Variables measured were sociodemographic characteristics, cigarette smoking, leisure time physical exercise, alcohol consumption and past history of cardiovascular disease.
Height and weight were measured at hospital admission, and
the body mass index (BMI) was calculated. Cigarette smoking
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
history involved questions about current or past use of cigarettes, and to be classified as an ex-smoker, a patient had to
report having quit smoking at least one year prior to the time of
the admission. Aspirin use was not investigated since it is not
used widely in Korea.
Dietary data were obtained by a nutritionist using a semiquantitative food frequency questionnaire (FFQ) containing 93
food items, as reported previously [8]. Each subject was asked
to state the number of meals eaten and the usual portion size
over the previous year. Consumption frequency was measured
on a nine-grade scale: never, once a month, twice a month, once
a week, three times a week, five times a week, once a day,
twice a day, three times a day. The questionnaire also included
a specific question about the type of fat used for cooking. This
information was also used in the appropriate recipes. During
the interview, food models and reference utensils were shown
to subjects to help them estimate portion size. The participants
were interviewed within a week of admission to the hospital
and were asked to describe their usual dietary patterns before
diagnosis of any known coronary disease. When it was apparent that a patient had substantially changed his usual dietary
pattern within the past year, we excluded him from the analysis.
Nutrient intake based on this information was calculated
using Korean food composition tables, while fatty acids were
calculated according to other published data [6, 10, 11]. To
calculate the daily nutrient intake, the nutrient content of each
food item was multiplied by the frequency of its daily consumption and all items summed. However, trans fatty acid and
folate intake could not be estimated because of the incomplete
database in Korea. The dietary method adopted was validated
by a pilot study, which was carried out on 31 men who visited
the hospital for health screening. Nutrient intakes estimated
from FFQ were compared with estimated nutrient intakes from
two three-day dietary records, and the results showed that the
method provided a reasonable measure of vitamin C as well as
total and specific types of fat [12]. The deattenuated Pearson
correlation coefficient for vitamin C was 0.65, which is comparable to those of other studies [13–15].
Statistical Analysis
Dietary vitamin C intake from food sources was categorized
into tertiles, which were based on the distribution of controls,
and the risk of non-fatal IHD in the highest and middle tertiles
was compared with the risk of non-fatal IHD in the lowest
tertile. The association between vitamin C intake and the risk of
non-fatal IHD was determined by multivariate logistic regression analysis. Also, we constructed a score variable for vitamin
C intake by awarding 1, 2 and 3 to the corresponding tertile
groups. Trend testing was performed by treating this score
variable as a continuous variable in the regression models.
Statistical significance (p ! 0.05) was the guideline for selecting independent variables to be included in the final logistic
regression model. The fiber intake was highly correlated with
373
Vitamin C Intake and Ischemic Heart Disease
the vitamin C intake (r " 0.84), and the change in the likelihood due to inclusion of the fiber intake was not significant.
Therefore, the fiber intake was not included in the final logistic
regression model in accordance with the parsimonious principle. No significant interactions were found between vitamin C
intake and smoking status, between vitamin C intake and BMI
or between smoking status and BMI. Therefore, we excluded
these interaction terms from the logistic regression model. The
analyses were adjusted for BMI (!25 kg/m2, !25 kg/m2),
smoking (#20 cigarettes/day, #20 cigarettes/day, ex-smoker,
nonsmoker), a past history of hypertension, a past history of
hyperlipidemia, energy, total fat or fatty acids, cholesterol, and
other antioxidants ("-carotene, vitamin E). We also performed
the same analysis upon subjects that did not use vitamin supplements. Finally, logistic regression was performed after excluding patients admitted to the department of ophthalmology
in order to examine whether or not the inclusion of patients
admitted to the department of ophthalmology could minimize the protective effect of vitamin C intake on the risk of
non-fatal IHD. Statistical analysis was performed using statistical analysis system (SAS) software (Release 8.1; SAS
Institute, Cary, NC).
RESULTS
Vitamin C tertiles, defined as vitamin C intake derived from
food !141.8 mg, 141.8 mg–220.2 mg, !220.2 mg were used
for the analysis. Details of the association between vitamin C
intake and selected baseline characteristics are presented in
Table 1. At higher vitamin C intake, men had higher BMIs and
had a lower past history of hyperlipidemia. Dietary intakes of
"-carotene, vitamin E and fiber as well as polyunsaturated fatty
acid (PUFA) and polyunsaturated fatty acid/saturated fatty acid
(P/S) were also higher at higher vitamin C intake.
The results of the multivariate analysis are shown in Table
2. Vitamin C intake was found to be inversely related to risk of
non-fatal IHD after adjustment for non-dietary variables. After
additional adjustment for energy, cholesterol and total fat (in
Model 2), and PUFA and saturated fatty acid (SFA) instead of
total fat (in Model 3), the above associations were retained. The
odds ratios (ORs) for the highest versus the lowest tertile were
0.26 (95% confidence interval (CI) 0.11– 0.65; p for trend "
0.00) for model 2, 0.25 (95% CI: 0.10 – 0.62; p for trend "
0.00) for model 3. Further adjustment for "-carotene and vitamin E led to only slight changes in the observed associations
(OR 0.36, 95% CI 0.13– 0.97, p for trend " 0.05 for Model 4;
OR 0.34, 95% CI 0.13– 0.90, p for trend " 0.04 for Model 5).
Logistic analysis was performed after adding the past history of
diabetes, alcohol consumption, exercise and omega-3 fatty acid
intake to the models. However, none of these variables was found
to be significantly related to non-fatal IHD. In addition, none of
these variables was capable of altering the significance of the
relationship between the vitamin C intake and non-fatal IHD.
In additional analysis of subjects that did not use vitamin
supplements, after adjusting for non-dietary risk factors and
energy, cholesterol and total fat (in Model 2) or fatty acid
intake (in Model 3) showed a significant difference between the
highest tertile and the lowest tertile. However, after additionally adjusting for "-carotene and vitamin E (in Model 4 and
Model 5), these risks were attenuated and no longer significant
(Table 3).
After excluding patients admitted to the department of ophthalmology, the odds ratios of non-fatal IHD in the highest
Table 1. Diet and Lifestyle Characteristics by Tertiles of Vitamin C Intake
Vitamin C intake tertile
Vitamin C (mg)
Age (year)
Body mass index (kg/m2)
Current smokers (%)
Regular exercise (%)
Current drinkers (%)
Past history of hypertension (%)
Past history of hyperlipidemia (%)
Average intake of Energy (kJ)
Total fat (% of energy)
PUFA (% of energy)
SFA (% of energy)
P/S
Cholesterol (mg/1000 kcal)
"-carotene (ug)
Vitamin E (mg)
Fiber (g)
!141.8 mg
(n " 92)
!220.2 mg
(n " 87)
!220.2 mg
(n " 71)
p-value
103.6
53.0
23.7
63.0
30.4
59.3
18.5
21.7
8532.2
22.8
5.1
7.1
0.77
133.4
3321.7
12.9
6.5
175.2
53.7
24.7
56.3
31.0
67.8
29.9
18.4
9784.1
23.3
5.1
7.2
0.74
139.4
4399.0
15.9
8.9
285.1
52.2
24.8
45.1
36.6
54.9
25.4
15.5
11253.4
23.5
5.5
7.2
0.84
131.4
8315.8
20.0
12.4
!0.01
0.36
0.03
0.22
0.67
0.57
0.51
0.02
!0.01
0.67
0.12
0.91
0.05
0.02
!0.01
!0.01
!0.01
PUFA " polyunsaturated fatty acid, SFA " saturated fatty acid, P/S " polyunsaturated fatty acid/saturated fatty acid.
374
VOL. 22, NO. 5
Vitamin C Intake and Ischemic Heart Disease
Table 2. Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for Non-Fatal Ischemic Heart Disease by Tertiles of Vitamin C
Intake (n " 250)
Vitamin C intake tertile
Model 11
Model 2:
Model 1
Model 3:
Model 1
Model 4:
Model 2
Model 5:
Model 3
1
!141.8 mg
2
!220.2 mg
3
!220.2 mg
p
for trend
1
1
0.74 (0.38–1.46)
0.67 (0.33–1.37)
0.35 (0.16–0.78)
0.26 (0.11–0.65)
0.01
0.00
1
0.64 (0.32–1.31)
0.25 (0.10–0.62)
0.00
1
0.73 (0.35–1.50)
0.36 (0.13–0.97)
0.05
1
0.73 (0.36–1.51)
0.34 (0.13–0.90)
0.04
$energy, total fat, cholesterol
$energy, PUFA, SFA, cholesterol
$"-carotene, vitamin E
$"-carotene, vitamin E
1
Model 1 included BMI (!25 kg/m2, !25 kg/m2), smoking (#20 cigarettes/day, #20 cigarettes/day, exsmokers, non smokers), past history of hypertension, and past
history of hyperlipidemia.
PUFA " polyunsaturated fatty acid, SFA " saturated fatty acid.
Table 3. Odds Ratios (ORs) and 95% Confidence Intervals (CIs) for Non-Fatal Ischemic Heart Disease by Tertiles of Vitamin C
Intake in the Subjects, Excluding Users of Vitamin Supplements (n " 228)
Vitamin C intake tertile
Model 11
Model 2:
Model 1
Model 3:
Model 1
Model 4:
Model 2
Model 5:
Model 3
1
!141.8 mg
2
!220.2 mg
3
!220.2 mg
p
for trend
1
1
0.77 (0.38–1.57)
0.71 (0.33–1.50)
0.38 (0.17–0.87)
0.29 (0.11–0.74)
0.02
0.01
1
0.69 (0.33–1.45)
0.28 (0.11–0.72)
0.01
1
0.79 (0.37–1.70)
0.42 (0.15–1.19)
0.12
1
0.79 (0.37–1.70)
0.40 (0.14–1.10)
0.09
$energy, total fat, cholesterol
$energy, PUFA, SFA, cholesterol
$"-carotene, vitamin E
$"-carotene, vitamin E
1
Model 1 included BMI (!25 kg/m2, !25 kg/m2), smoking (#20 cigarettes/day, #20 cigarettes/day, exsmokers, non smokers), past history of hypertension, and past
history of hyperlipidemia.
PUFA " polyunsaturated fatty acid, SFA " saturated fatty acid.
tertile of vitamin C intake compared with those in the lowest
tertile ranged from 0.28 to 0.47, a little higher than those
obtained from logistic models that included patients admitted to
the department of ophthalmology, as shown Table 2 (the odds
ratios: 0.25– 0.36).
Further analyses were undertaken involving combinations
of factors (i.e., smoking status) that may influence the vitamin
C intake level. A positively strong association was seen at
higher smoking levels. Compared to current smokers in the
lowest vitamin C tertile, the ORs of non-fatal IHD among
ex-smoking men and among non-smoking men in the highest
vitamin C tertile were 0.24 (95% CI 0.07– 0.88) and 0.12 (95%
CI 0.02– 0.77) respectively (Fig. 1).
DISCUSSION
We observed an inverse association of vitamin C intake
with risk of non-fatal IHD in Korean men. For dietary vitamin
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
C the relation remained significant after adjustment for BMI,
smoking, past history of hypertension, past history of hyperlipidemia, energy, total fat, SFA, PUFA, "-carotene and vitamin E. Our results are consistent with those of several other
studies [16 –19] that found dietary vitamin C or plasma vitamin
C to be associated with a protective effect against IHD. Knekt
et al. [20] reported an inverse association between the vitamin
C intake and IHD among women, but not among men. However, others have observed no association between high vitamin
C intake or high plasma vitamin C and IHD [21–27]. KlipsteinGrobusch et al. (#126 mg/day) [25], Kushi et al. (!196
mg/day) [26], and Enstrom et al. (!250 mg/day) [27] reported
no additional reduction in risk of IHD associated with a relatively high vitamin C intake. Furthermore, Levine et al. [28]
suggested that because plasma and circulating cells become
saturated between 200 mg and 400 mg of vitamin C, increasing
vitamin C intake over this amount might have no additional
effect on disease risk. However, we found that higher vitamin
375
Vitamin C Intake and Ischemic Heart Disease
Fig. 1. Odds ratios of non-fatal ischemic heart disease by tertiles of vitamin C intake at different smoking statuses (Model included BMI (!25 kg/m2,
!25 kg/m2), past history of hypertension, past history of hyperlipidemia, energy, polyunsaturated fatty acid, saturated fatty acid, cholesterol,
"-carotene, and vitamin E intake).
C intake (!220 mg/day) was significantly associated with a
decreased risk of non-fatal IHD. The difference between our
study and other studies may have resulted from the difference
in the range of vitamin C intake or plasma concentrations and
the prevalence of smoking.
Smokers have a higher vitamin C requirement than nonsmokers, due to their lower dietary intakes [9, 29, 30], and their
higher metabolic turnovers of vitamin C [31]. Smokers in
general have poorer diets than nonsmokers; they eat more fat
and SFA and consume fewer antioxidants and fiber than nonsmokers. Although the RDA of vitamin C for smokers is 125
mg in U.S.A. [32], Schectman et al. [33] proposed that smokers
should consume more than 200 mg of vitamin C, and Kallner
et al. [31] suggested that at least 140 mg of vitamin C is
required by smokers to reach serum vitamin C concentrations
comparable with those of nonsmokers. The prevalences of
smokers in Western studies, which showed no protective effects of vitamin C on IHD, were 20% to 31% [25], 12% to 22%
[26] and 38% [27], and these were much lower those in Asian
countries, which showed 63% for China (in 1996) and 53% for
Japan (in 1998) [34]. The high smoking prevalence in Korea [4]
makes it an important risk factor. The percentage of current
smokers in this study was 64.8% for cases and 48.6% for
controls. Therefore, the protective effects of higher vitamin C
intake (!220 mg/day) in this study may suggest that there is a
possibility of biological interaction between vitamin C intake
and smoking.
Recognized risk factors for IHD were evident in this study
[8]. Men who reported the following risk factors had higher
risks of IHD than men without these risk factors: BMI (!25
kg/m2, OR 2.26; 95% CI 1.27– 4.01), current smoking (#20
cigarettes/day, OR 10.51; 95% CI 3.61–30.56) and total fat
intake (OR 1.08; 95% CI 1.02–1.14). Because the data we
collected are observational, we evaluated whether those association with IHD could be explained by other healthy lifestyle
376
practices among men with the highest tertile of vitamin C
intake. In our study, men with the highest tertile of vitamin C
had a lower smoking rate, and different PUFA, P/S and cholesterol intakes as well as a past history of hypertension and
hyperlipidemia. The information we collected on blood pressure, serum triglyceride and serum cholesterol levels after
admission was not used because these could have been modified by cardiovascular event or treatment. Instead of these
variables, we used a past history of hyperlipidemia and hypertension. To account for the effects of potentially confounding
lifestyle factors, we adjusted for dietary and non-dietary risk
factors. When non-dietary risk factors were adjusted, the association between vitamin C intake and risk of non-fatal IHD was
similar to that obtained when only age was adjusted. On the
other hand, when dietary variables were additionally adjusted
by multiple regression, the intake of total fat or subtype of fat
were found to have more important confounding effects. This
actually strengthened the association between vitamin C intake
and non-fatal IHD (OR 0.26; 95% CI 0.11– 0.65 controlling for
total fat, OR 0.25; 95% CI 0.10 – 0.62 controlling for fat subtype). In our study, alcohol intake, exercise, the history of
diabetes and omega-3 fatty acid intake were not risk factors for
non-fatal IHD. This was unexpected. It is possible that the
power of this study was insufficient to detect the differences in
these factors between the cases and controls. Further research
will be needed to determine whether or not these factors are
associated with non-fatal IHD in a population with a high
prevalence of smoking.
In our case-control study, cases were selected with newly
developed acute MI as confirmed by ECG, enzyme, cardiac
pain, and angina pectoris were confirmed by angiography,
while controls were selected from patients at the departments of
ophthalmology and orthopedic surgery. The use of incident
cases helped to avoid the possibility that cases may have
modified their dietary pattern because of a previous diagnosis
VOL. 22, NO. 5
Vitamin C Intake and Ischemic Heart Disease
of IHD. However, this study was limited in terms of selecting
the controls admitted to the department of ophthalmology since
they might have had low antioxidant level and intake. The
distributions of controls admitted to the department of ophthalmology were 54 for cataract, 7 for glaucoma, 7 for retinopathy
and 5 for other eye diseases, and the patients admitted to the
department of orthopedic surgery were 27 for trauma, 14 for
degenerative disease and 32 for inflammatory disease. After
excluding the patients admitted to the department of ophthalmology, the main result on the relationship between the vitamin
C intake and the risk of non-fatal IHD was not changed.
Therefore, the inclusion of ophthalmologic patients among our
controls does not seem to minimize the protective effect of
vitamin C intake. In order to reduce the potential for recall bias,
a highly structured questionnaire was used, and the dietary
interview was performed within a week of hospitalization using
food models and reference utensils. Moreover, the cases and
controls were blind to the study hypothesis, as were the interviewers. However, the recall bias might not have been eliminated perfectly in our study design. Care should be taken when
interpreting the effect of the vitamin C intake on non-fatal IHD.
This relationship between vitamin C intake and IHD may
also be affected by other potentially important micronutrients;
for example, foods rich in vitamin C also contain "-carotene
and vitamin E [35], and people taking vitamin supplements are
generally more health-conscious than others, although those
with vitamin deficiencies may be ill or have detrimental health
habits. When adjusted for other antioxidants, the above associations were not changed, though a little attenuated (OR 0.34,
95% CI 0.13– 0.90). The supplemental use of vitamins has also
been shown to be related to IHD mortality [36, 37]. We
requested details of the type and dose of multivitamin and
vitamin C supplementations in the FFQ; however, the effect of
vitamin supplements could not be analyzed in detail because of
the low prevalence of vitamin supplement use (8.8%; 22 of 250
subjects). When we conducted additional analyses after excluding subjects who had used multivitamins and vitamin C supplements, the association between vitamin C intake and the risk
of non-fatal IHD remained significant, except when we additionally controlled for "-carotene and vitamin E, which, in
themselves, showed no significant inverse association. One
limitation to our study is the effect of the fiber intake. We could
not exclude this effect because of the multicollinearity between
the vitamin C intake and fiber intake.
Although no significant statistical interaction was found
between vitamin C intake and smoking status in this study, we
conducted further analyses involving combinations of the two
risk factors (vitamin C intake and smoking status). When the
two factors were examined in combination, the risk of non-fatal
IHD (OR 0.12; 95% CI 0.02– 0.77) was lowest among those
that had the highest intake of vitamin C intake and were
nonsmokers. This can be explained by the following biological
interaction: Smoking may cause an increased turnover of vitamin C because it induces oxidative stress; this would lower
JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION
vitamin C concentrations and increase cardiovascular disease
risk [30, 38]. On the basis of such a mechanism, it would
appear that smokers in particular, may benefit from increased
vitamin C intake.
CONCLUSION
This study indicates the importance of vitamin C intake as
well as smoking cessation on the prevention of IHD in developing countries, where the prevalence of smoking is high. In
addition, this finding suggests that the effect of vitamin C
intake on non-fatal IHD incidence may differ according to the
degree of oxidative stress induced by factors such as smoking.
Randomized trials are needed to provide recommended dietary
allowances of vitamin C in a population with a high prevalence
of smoking.
ACKNOWLEDGMENT
This research was supported in part by Basic Research
Medical Fund Ministry of Education, Korea for 1995. The
authors especially thank Dr. Walter Willett for his valuable
comments to this paper.
REFERENCES
1. Carr AC, Frei B: Toward a new recommended dietary allowance
for vitamin C based on antioxidant and health effects in humans.
Am J Clin Nutr 69:1086–1087, 1999.
2. Dibble DL: Antioxidant consumption and risk of coronary heart
disease: emphasis on vitamin C, vitamin E, and "-carotene, A
statement for healthcare professionals from the American Heart
Association. Circulation 99:591–595, 1999.
3. Simon JA: Vitamin C and cardiovascular disease: a review. J Am
Coll Nutr 11:107–125, 1992.
4. Suh I: Cardiovascular mortality in Korea: a country experiencing
epidemic transition. Acta Cardiol 56:75–81, 2001.
5. Ministry of Health & Social Welfare: “Report on 1998 National
Health and Nutrition Survey.” Seoul, Republic of Korea, 1999.
6. The Korean Nutrition Society: “Recommended Dietary Allowances for Koreans.” Seoul, Republic of Korea, 2000.
7. Jee SH, Suh I, Kim IS, Appel LJ: Smoking and atherosclerotic
cardiovascular disease in men with low levels of serum cholesterol:
the Korea medical insurance corporation study. JAMA 282:2149–
2155, 1999.
8. Suh I, Oh KW, Lee KH, Psaty BM, Nam CM, Kim SI, Gang HG,
Cho SY, Shim WH: Moderate dietary fat consumption as a risk
factor for ischemic heart disease in a population with a low fat
intake: a case-control study in Korean men. Am J Clin Nutr
73:722–727, 2001.
9. Dallongeville J, Marecaux N, Fruchart JC, Amouyel P: Cigarette
smoking is associated with unhealthy patterns of nutrient intake: a
meta-analysis. J Nutr 128:1450–1457, 1998.
377
Vitamin C Intake and Ischemic Heart Disease
10. Ministry of Health & Social Welfare: “Korean Food Composition
Table.” Seoul, Republic of Korea, 1996.
11. Lee YC, Lee HJ, Oh KW: “Fatty Acid Composition of Korean
Foods.” Seoul, Republic of Korea: Shin Kwang Publisher, 1995.
12. Shim JS, Kim MY, Oh KW, Yoon JY, Nam CM, Suh I: Validity
assessment for Korean semi food frequency questionnaire [Abstract]. Korean J Prev Med, 2000.
13. Pietinen P, Hartman AM, Haapa E, Rasanen L, Haapakoski J,
Palmgren J, Albanes D, Virtamo J, Huttunen JK: Reproducibility
and validity of dietary assessment instruments. Am J Epidemiol
128:667–676, 1988.
14. Rimm EB, Giovannucci EL, Stampfer MJ, Colditz GA, Litin LB,
Willett WC: Reproducibility and validity of an expended selfadministered semiquanititative food frequency questionnaire
among male health professionals. Am J Epidemiol 135:1114–
1126, 1992.
15. Martinez ME, Marshall JR, Graver E, Whitacre RC, Woolf K,
Ritenbaugh C, Alberts DS: Reproducibility and validity of a selfadministered food frequency questionnaire in a chemoprevention
trial of adenoma recurrence. Cancer Epidemiol Biomarkers Prev
8:941–946, 1999.
16. Simon JA, Hudes ES, Tice JA: Relation of serum ascorbic acid to
mortality among US adults. J Am Coll Nutr 20:255–263, 2001.
17. Nyyssonen K, Parviainen MT, Salonen R, Tuomilehto J, Salonen
JT: Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland. BMJ
314:634–638, 1997.
18. Sahyoun NR, Jacques PF, Russel RM. Carotenoids, vitamin C and
E and mortality in an elderly population: Am J Epidemiol 144:
501–511, 1996.
19. Enstrom JE, Kanim LE, Klein MA: Vitamin C intake and mortality
among a sample of the United States population. Epidemiology
3:194–202, 1992.
20. Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M,
Aromaa A: Antioxidant vitamin intake and coronary mortality in a
longitudinal population study. Am J Epidemiol 139:1180–1189,
1994.
21. Pandey DK, Shekelle R, Selwyn BJ, Tangney C, Stamler J: Dietary
vitamin C and "-carotene and risk of death in middle-aged men:
The Western Electric study. Am J Epidemiol 142:1269–1278,
1995.
22. Loria CM, Klag MJ, Caulfeild LE, Whelton PK: Vitamin C status
and mortality in US adults. Am J Clin Nutr 72:139–145, 2000.
23. Gale CR, Martyn CN, Winter PD, Cooper C: Vitamin C and risk
of death from stroke and coronary heart disease in cohort of elderly
people. BMJ 310:1563–1566, 1995.
24. Riemersma RA, Wood DA, Macintyre CCA, Elton RA, Gey KF,
378
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
Oliver MF: Risk of angina pectoris and plasma concentrations of
vitamin A, C, and E and carotene. Lancet 337:1–5, 1991.
Klipstein-Grobusch K, Geleijnse JM, den Breeijen JH, Boeing H,
Hofman A, Grobbee DE, Witteman JCM: Dietary antioxidants and
risk of myocardial infarction in the elderly: the Rotterdam study.
Am J Clin Nutr 69:261–266, 1999.
Kushi LH, Folsom SR, Prineas RJ, Mink PJ, Wu Y, Bostick RM:
Dietary antioxidant vitamins and death from coronary heart disease
in postmenopausal women. N Engl J Med 334:1156–1162, 1996.
Enstrom JE, Kanim LE, Breslow L: The relationship between
vitamin C intake, general health practices and mortality in Alameda County, California. Am J Public Health 76:1124–1130, 1986.
Levine M, Wang Y, Padayatty SJ, Morrow J: A new recommended
dietary allowance of vitamin C for healthy young women. Proc
Natl Acad Sci 98:9842–9846, 2001.
Lykkesfeldt J, Christen S, Wallock LM, Chang HH, Jacob RA,
Ames BN: Ascorbate is depleted by smoking and repleted by
moderate supplementation: a study in male smokers and non smokers with matched dietary antioxidant intakes. Am J Clin Nutr
71:530–536, 2000.
Ma J, Hampl JS, Betts NM: Antioxidant intakes and smoking
status: data from the continuing survey of food intakes by individuals 1994–1996. Am J Clin Nutr 71:774–780, 2000.
Kallner AB, Hartmann D, Horing DH: On the requirement ascorbic
acid in man: steady-state turnover and body pool in smokers. Am J
Clin Nutr 34:1347–1355, 1981.
Food and nutrition board and panel on dietary antioxidants and
related compounds. Vitamin C 5:95–185, 2000.
Schectman G, Byrd JC, Hoffman R: Ascorbic acid requirements
for smokers: analysis of a population survey. Am J Clin Nutr
53:1466–1470, 1991.
Corrao A, Guindon GE, Sharma N, Shokoohi DF (eds): “Tobacco
Control Country Profiles” [The 11th World Conference on Tobacco and Health]. Atlanta: The American Cancer Society, 2000.
Weisburger JH: Nutritional approach to cancer prevention with
emphasis on vitamins, antioxidants, and carotenoids. Am J Clin
Nutr 53 (Suppl 1):226S–237S, 1991.
Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA,
Willett WC: Vitamin E consumption and the risk of coronary heart
disease in men. N Engl J Med 328:1450–1456, 1993.
Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B,
Willett WC: Vitamin E consumption and the risk of coronary heart
disease in women. N Engl J Med 328:1444–1449, 1993.
Lykkesfeldt J, Loft S, Lielsen JB, Poulsen HE: Ascorbic acid and
dehydroascorbic acid as biomarkers of oxidative stress caused by
smoking. Am J Clin Nutr 65:959–963, 1997.
Received April 3, 2002; revision accepted April 4, 2003.
VOL. 22, NO. 5