Article

Soda consumption and the risk of stroke in men and women

Harvard University, Cambridge, Massachusetts, United States
American Journal of Clinical Nutrition (Impact Factor: 6.77). 04/2012; 95(5):1190-9. DOI: 10.3945/ajcn.111.030205
Source: PubMed
ABSTRACT
Consumption of sugar-sweetened soda has been associated with an increased risk of cardiometabolic disease. The relation with cerebrovascular disease has not yet been closely examined.
Our objective was to examine patterns of soda consumption and substitution of alternative beverages for soda in relation to stroke risk.
The Nurses' Health Study, a prospective cohort study of 84,085 women followed for 28 y (1980-2008), and the Health Professionals Follow-Up Study, a prospective cohort study of 43,371 men followed for 22 y (1986-2008), provided data on soda consumption and incident stroke.
We documented 1416 strokes in men during 841,770 person-years of follow-up and 2938 strokes in women during 2,188,230 person-years of follow-up. The pooled RR of total stroke for ≥ 1 serving of sugar-sweetened soda/d, compared with none, was 1.16 (95% CI: 1.00, 1.34). The pooled RR of total stroke for ≥ 1 serving of low-calorie soda/d, compared with none, was 1.16 (95% CI: 1.05, 1.28). Compared with 1 serving of sugar-sweetened soda/d, 1 serving of decaffeinated coffee/d was associated with a 10% (95% CI: 1%, 19%) lower risk of stroke and 1 serving of caffeinated coffee/d with a 9% (95% CI: 0%, 17%) lower risk. Similar estimated reductions in risk were seen for substitution of caffeinated or decaffeinated coffee for low-calorie soda.
Greater consumption of sugar-sweetened and low-calorie sodas was associated with a significantly higher risk of stroke. This risk may be reduced by substituting alternative beverages for soda.

Full-text

Available from: Kathryn M Rexrode
Soda consumption and the risk of stroke in men and women
1–3
Adam M Bernstein, Lawrence de Koning, Alan J Flint, Kathryn M Rexrode, and Walter C Willett
ABSTRACT
Background: Consumption of sugar-sweetened soda has been as-
sociated with an increased risk of cardiometabolic disease. The re-
lation with cerebrovascular disease has not yet been closely
examined.
Objective: Our objective was to examine patterns of soda consump-
tion and substitution of alternative beverages for soda in relation to
stroke risk.
Design: The Nurses’ Health Study, a prospective cohort study of
84,085 women followed for 28 y (1980–2008), and the Health Pro-
fessionals Follow-Up Study, a prospective cohort study of 43,371
men followed for 22 y (1986–2008), provided data on soda con-
sumption and incident stroke.
Results: We documented 1416 strokes in men during 841,770 per-
son-years of follow-up and 2938 strokes in women during 2,188,230
person-years of follow-up. The pooled RR of total stroke for 1
serving of sugar-sweetened soda/d, compared with none, was 1.16
(95% CI: 1.00, 1.34). The pooled RR of total stroke for 1 serving
of low-calorie soda/d, compared with none, was 1.16 (95% CI: 1.05,
1.28). Compared with 1 serving of sugar-sweetened soda/d, 1 serv-
ing of decaffeinated coffee/d was associated with a 10% (95% CI:
1%, 19%) lower risk of stroke and 1 serving of caffeinated coffee/
d with a 9% (95% CI: 0%, 17%) lower risk. Similar estimated
reductions in risk were seen for substitution of caffeinated or de-
caffeinated coffee for low-calorie soda.
Conclusions: Greater consumption of sugar-sweetened and low-
calorie sodas was associated with a significantly higher risk of
stroke. This risk may be reduced by substituting alternative bever-
ages for soda. Am J Clin Nutr 2012;95:1190–9.
INTRODUCTION
Consumption of sugar-sweetened beverages, including sodas,
vitamin water, and energy drinks, has increased in the United
States over the past 3 decades. Per capita consumption in 2009
was estimated at 45 gallons/y, or nearly half of the total beverage
intake (1). Sodas, or carbonated soft drinks, are consumed more
than any other sugar-sweetened beverage and, despite a recent
report that intake of sugar-sweetened soda in the United States
may be declining, soda remains the largest source of added sugar
in the diet (2).
Sugar-sweetened beverages have been linked with weight
gain, diabetes, hypertension, hyperlipidemia, gout, and coronary
artery disease (CAD)
4
(3–7). The associations with cardiome-
tabolic disease appear to be independent of BMI and energy intake,
which suggests that other mechanisms, such as hyperglycemia,
dyslipidemia, inflammation, or endothelial dysfunction, underlie
the association (6). Low-calorie sodas are less-well studied than
are sugar-sweetened sodas. Although intake of these beverages
was recently linked with the metabolic syndrome, reverse cau-
sality or residual confounding could explain the association (8),
and a recent prospective study found no association between
low-calorie soda intake and diabetes risk (9). Intake of low-
calorie soda has been associated with progression of kidney
disease (10).
Given the associations between soda consumption, car-
diometabolic risk factors, and CAD, we sought to evaluate the
relation between sodas and stroke risk. This relation has not been
closely examined, yet stroke remains a significant cause of
morbidity, mortality, and health care expenditures in the United
States (11, 12) and shares many of the same risk factors as CAD
(13). We therefore examined patterns of soda consumption and
the substitution of alternative beverages for soda in relation to
stroke risk in 2 large prospective cohorts of men and women.
SUBJECTS AND METHODS
Study populations
The Nurses’ Health Study (NHS) began in 1976, when 121,700
female registered nurses aged 30–55 y residing in the United
States provided information on their medical history and lifestyle.
The Health Professionals Follow-Up Study (HPFS) began in
1986, when 51,529 male dentists, pharmacists, optometrists,
osteopaths, podiatrists, and veterinarians aged 40–75 y and re-
siding in the United States provided information on their medical
history and lifestyle. Every 2 y, follow-up questionnaires have
been sent to both populations to update their information. In
1
From the Wellness Institute of the Cleveland Clinic, Lyndhurst, OH
(AMB); and the Departments of Nutrition (AMB, AJF, LdK, and WCW)
and Epidemiology (AJF and WCW), Harvard School of Public Health, and
the Channing Laboratory (AJF and WCW) and Division of Preventive Med-
icine (KMR), Department of Medicine, Brigham and Women’s Hospital and
Harvard Medical School, Boston, MA.
2
Supported by grants P01CA087969 and U19 CA055075-20 from the
NIH, Department of Health and Human Services. AMB was supported
through the Harvard Human Nutrition Program.
3
Address correspondence and reprint requests to AM Bernstein, Wellness
Institute of the Cleveland Clinic, 1950 Richmond Road/TR2-203, Lyndhurst,
OH 44124. E-mail: bernsta2@ccf.org.
4
Abbreviations used: CABG, coronary artery bypass grafting; CAD, cor-
onary artery disease; FFQ, food-frequency questionnaire; HPFS, Health Pro-
fessionals Follow-Up Study; NHS, Nurses’ Health Study; PCI, percutaneous
coronary intervention.
Received November 5, 2011. Accepted for publication February 10, 2012.
First published online April 4, 2012; doi: 10.3945/ajcn.111.030205.
1190 Am J Clin Nutr 2012;95:1190–9. Printed in USA. Ó 2012 American Society for Nutrition
Page 1
1980, a 61-item food-frequency questionnaire (FFQ) was in-
cluded to assess intake of specific foods in the NHS. Expanded
questionnaires updated dietary intake in 1986, 1990, 1994, 1998,
2002, and 2006. In 1986, a 131-item FFQ assessed intake of
specific foods in the HPFS, and similar questionnaires were used
to update dietary intake in 1990, 1994, 1998, 2002, and 2006. As
in our previous analyses, we excluded participants who left
excessive items blank on their baseline FFQ, those who reported
implausibly low or high energy intakes, and those with previously
diagnosed cancer, diabetes, angina, myocardial infarction, stroke,
or other cardiovascular disease [including a history of percuta-
neous coronary intervention (PCI) or coronary artery bypass
grafting (CABG)] (14–18). The final 1980 baseline population
consisted of 84,085 women, and the final 1986 baseline pop-
ulation consisted of 43,371 men. This study was approved by the
Committee on the use of Human Subjects in Research at Brigham
and Women’s Hospital. Return of a questionnaire was considered
to imply consent.
Assessment of soda intake
The types of sodas on the FFQs included low-calorie cola with
caffeine (eg, Diet Coke, Tab with caffeine), low-calorie cola
without caffeine (eg, Pepsi Free), other low-calorie carbonated
beverages (eg, Diet 7-Up, Fresca, Diet Mountain Dew, diet ginger
ale), sugar-sweetened cola with caffeine (eg, Coke, Pepsi), sugar-
sweetened cola without caffeine (eg, caffeine-free Coke, caffeine-
free Pepsi), and other carbonated beverages with sugar (eg, 7-Up,
Mountain Dew, Surge, Dr Pepper). We categorized soda as sugar-
sweetened or low-calorie (diet or artificially sweetened). Colas
are a type of soda, or carbonated soft drink, originally made with
kola nuts to add caffeine. To calculate each participant’s soda
intake, the participant was asked how often on average during the
previous year he or she had consumed one glass, bottle, or can.
Nine responses were possible, ranging from “never or almost
never” to “more than 6 times per day.” The reproducibility and
validity of the FFQs in measuring beverage intake were pre-
viously described (19–23): the Pearson correlation coefficient,
corrected for within-person variation, between the FFQ and di-
etary records was previously reported as 0.84 for cola and 0.36–
0.40 for noncola soda (21).
Ascertainment of incident stroke cases
The primary endpoint for this study was incident stroke oc-
curring after the return of the 1980 FFQ but before 1 June 2008 in
the NHS and after the return of the 1986 FFQ but before 31
January 2008 in the HPFS. After report of a stroke, permission to
obtain medical records was requested, and these were reviewed
by study physicians with no knowledge of the subjects’ self-
reported risk factor status. Stroke was classified as ischemic
(thrombotic, embolic, or nonhemorrhagic), hemorrhagic (intra-
parenchymal hemorrhage or subarachnoid hemorrhage), or of
unknown type, as per criteria in the National Survey of Stroke
(24). Nonfatal strokes for which confirmatory information was
obtained by interview or letter but no medical records and no
neuro-imaging (computerized tomography or magnetic reso-
nance imaging) were available, were designated as probable [225
of 1111 (or 20%) of cases in men and 737 of 2379 (or 31%) of
cases in women]. Deaths were identified from state vital records
or the National Death Index or were reported by next of kin or the
postal system. Follow-up for deaths was shown to be .98%
complete (25). Stroke was confirmed as fatal only if confirmed
by medical records or autopsy report. Fatal stroke was desig-
nated as probable if stroke was reported on the death certificate
or reported by next of kin, but no medical records were avail-
able. These cases constituted 98 of 305 (or 32%) cases in men
and 236 of 560 (or 42%) cases in women. We included all
confirmed and probable cases in our report because results were
similar after probable cases were excluded.
Statistical analysis
We first assessed whether a report of intermediate outcomes
(diabetes, hypertension, hypercholesterolemia, angina, or
CABG/PCI), myocardial infarction, or cancer were associated
with a subsequent change in sugar-sweetened or low-calorie soda
intake (see online supplementary material under “Supplemental
data” in the online issue). These associations were weak; thus,
these diagnoses could not be important time-dependent con-
founders. Therefore, to avoid misclassification of participants’
long-term soda intake, we continued updating each participant’s
intake throughout follow-up using data from all repeated FFQs.
To reduce within-person variation and best represent long-term
diet, participants were divided into categories of cumulative
average intake of sugar-sweetened and low-calorie soda con-
sumption. The categories included none, up to once per week,
once per week up to once per day, and once per day or more.
Cumulative averages were calculated by taking the mean of all
reported FFQ intakes up to the beginning of a follow-up interval.
The cumulative average intake was then associated with stroke
incidence from the time of the last returned questionnaire until
the next follow-up cycle. If dietary data from a particular FFQ
was missing, then that cycle’s cumulative average was the last
cumulative average carried forward.
We evaluated the associations between sugar-sweetened and
low-calorie soda consumption and total stroke incidence (is-
chemic, intraparenchymal hemorrhage, subarachnoid hemor-
rhage, and unknown type) and the incidence of hemorrhagic and
ischemic strokes. Because the American Heart Association and
American Stroke Association have developed guidelines for the
primary prevention of stroke (inclusive of both ischemic and
hemorrhagic subtypes), and because of the recognized overlap of
risk factors and prevention strategies, we evaluated the associ-
ation between soda consumption and total stroke (26). In the
NHS, person-years of follow-up were calculated from the return
of the 1980 FFQ to the date of the first stroke event, death, or 1
June 2008, whichever came first. In the HPFS, person-years of
follow-up were calculated from the return of the 1986 FFQ to the
date of the first stroke event, death, or 31 January 2008,
whichever came first. The RR was computed by using a multi-
variable Cox proportional hazards regression model, with the
incidence rate in a specific category of cumulative average soda
intake divided by that in the lowest category (none). All models
were mutually adjusted for the other beverage type; ie, the sugar-
sweetened soda analysis adjusted for low-calorie soda and vice
versa. The first multivariate model was stratified on age (mo) and
calendar time (2-y time intervals) and included red meat, poultry,
fish, whole-fat dairy products, low-fat dairy products, and nuts
(all in servings/d) and simultaneously controlled for intakes of
SODA AND STROKE RISK 1191
Page 2
cereal fiber (g/d), alcohol (g/d), fruit and vegetable intake
(servings/d), and trans unsaturated fatty acids (g/d) and other
potential nondietary confounding variables. These variables
were updated biennially and included physical exercise (,3, 3
to ,9, 9 to ,18, 18 to ,27, or 27 metabolic equivalent tasks/
wk), cigarette smoking [never, past, or current (1–14, 15–24, or
25 cigarettes/d)], menopausal status in women (premenopausal,
postmenopausal with no history of hormone replacement, post-
menopausal with a history of hormone replacement, or post-
menopausal with current hormone replacement), parental history
of early myocardial infarction (before age 60 y), years of multi-
vitamin use, vitamin E supplement use (yes or no), and aspirin use
at least once per week (yes or no). The last value was carried
forward for one 2-y cycle to replace missing values. If partici-
pants left excessive items blank on a follow-up questionnaire, or
reported implausibly high or low energy intakes, they were con-
sidered to be missing data from that particular questionnaire, and
their most recent value (of physical exercise, for instance) was
carried forward. If the last value was missing, a missing value
indicator was created. The median value for each category of
intake was used to test for a linear tre nd across categorie s.
Neither a diagnosis of diabetes, angina, hypertension, hyper-
cholesterolemia, CABG/PCI, or myocardial infarction nor the
use of the med ications prescribed to treat these diseases (in-
cluding statins and b-blockers) was i nclud ed, because all of
these may be co nsidered intermedia te outcomes on the causal
pathway between diet and stroke. In a second multiva riate
model, we inc luded the above covariate s as well as total energy
(kcal) and BMI (in kg/m
2
; ,22, 22–24, 24–25, 25–27, 27–29,
29–30, 30–32, 32–35, 35–40, or .40),bothofwhichmaybe
considered either confounders or intermedia tes on the causal
pathway between soda consumption and stroke. RRs and SEs
for each category of intake from each cohort were then pooled
in fixed-effects m odels to arrive at summary estimates as the Q
statistic P value for be tween- study heter ogeneity was not sta -
tistically significant (null hypothesis is tha t t here is no het-
erogeneity between the HPFS and the NHS). To estima te the
absolute risk of total stroke by category of soda intake, we
multiplied the multivariable RRs by the incidence rates in t he
referent groups (cases/per 100,000 person-years) (27).
In sensitivity analyses, to assess whether metabolic changes
related to excess body weight before the onset of cohort follow-
up influenced potential low-calorie soda–stroke associations, we
adjusted our multivariate models for weight change (increase or
decrease) in the 5 y before 1986 for men and in the 4 y before
1980 for women. We evaluated the relation between soda intake
and subarachnoid hemorrhage in a multiv ariate model. To evaluate
whether a soda-stroke association was mediated or confounded by
the presence of hypertension or diabetes, we adjusted our multi-
variate models for these diseases. Separately, we stratified our
multivariate model on the presence of diabetes (yes or no) or
hypertension (yes or no) to assess for ef fect modification of soda
intake by one of these diagnoses. We tested the significance of the
interaction with a likelihood ratio test by comparing a model with
the interaction terms to a model with only the main effects.
We also estimated the RR of stroke associated with substituting
caffeinated coffee, decaffeinated coffee, water, tea, skim milk, or
orange juice for either sugar-sweetened or lo w-calorie soda. To do
so, we fit multiv ariable Cox proportional hazards models, which
included the cov ariates from our multivariable model with energy
intake and BMI, plus the above beverages entered as continuous
variables rather than as categorical variables (cumulative av-
erage servings/d). The cumulative average intakes of caffein-
ated coffee, deca ffeinat ed coffee, water, t ea, skim milk, or
orange juice were calculatedinthesamewayasforsoda.
Decaffeinated coffe e was first asked about in the NHS in 1984,
and water was first asked about in 1986. The difference in the
coefficients of 2 beverages, plus their covariance, was used to
estimate the RR and variance for the substitution (28, 29). RRs
and variances for each substitution from each cohort were then
poole d in fixed-effect s models to arrive at a summary e stimate
of th e effect of substituting one beverage for another in rela tion
to total stroke r isk. All P values are 2-sided, with P val ues
,0.05 considered statistically significant.
RESULTS
Cohort characteristics
During 2,188,230 person-years of follow-up from 1980 through
2008 in the NHS and during 841,770 person-years of follow-up
from 1986 through 2008 in the HPFS, we documented 2938 strokes
in women (1513 ischemic, 267 intraparenchymal hemorrhages,
252 subarachnoid hemorrhages, and 906 unspecified) and 1416
strokes in men (843 ischemic, 163 intraparenchymal hemorrhages,
54 subarachnoid hemorrhages, and 356 unspecified). Our follow-
up rate through 2006 (defined as person-years contributed by study
participants until their last returned FFQ or death divided by
person-years contributed by study participants until death) was
96% in men and 97% in women. Characteristics of the study
participants during follow-up, averaged according to the pro-
portion of person-time in each category of soda intake, are shown
in Tables 1 and 2. Compared with men and women who did not
consume sugar-sweetened soda, those who consumed 1 serving/
d had higher rates of hypertension and hypercholesterolemia and
lower physical activity. More frequent consumption of sugar-
sweetened soda was associated with more frequent consumption
of red meat and whole-fat dairy products. A higher consumption
of low-calorie soda consumption was also associated with higher
rates of chronic disease and a higher BMI.
Soda intake and total incident stroke
In multivariable analyses adjusted for dietary and nondietary
cardiovascular disease risk factors, higher intakes of both sugar-
sweetened and low-calorie soda were associated with a higher
risk of overall stroke (Table 3). In men, 1 serving sugar-
sweetened soda/d, compared with none, was associated with
a statistically nonsignificant RR of total stroke of 1.08 (95% CI:
0.82, 1.41); in women, the statistically significant RR was 1.19
(95% CI: 1.00, 1.42). These risks corresponded to absolute risk
differences of 14 and 24 cases/100,000 person-years. In men,
1 serving low-calorie soda/d, compared with none, was asso-
ciated with an RR of total stroke of 1.10 (95% CI: 0.92, 1.32); in
women, it was 1.18 (95% CI: 1.05, 1.33). These RRs corre-
sponded to absolute risk differences of 17 and 21 cases/100,000
person-years. Pooled multivariable risk of stroke among men
and women was 1.12 (95% CI: 1.02, 1.24) for 1 serving sugar-
sweetened soda/d and 1.09 (95% CI: 1.04, 1.15) for 1 serving
low-calorie soda. Risk of stroke with consumption of either
sugar-sweetened or low-calorie soda was greater in women than
in men, but the results of formal tests of heterogeneity comparing the
1192 BERNSTEIN ET AL
Page 3
TABLE 1
Age-standardized characteristics of 84,085 women in the Nurses’ Health Study, 1980–2008
Low-calorie soda consumption Sugar-sweetened soda consumption
None
None up to
once per week
Once per week up
to once per day
Once per
day or more None
None up to
once per week
Once per week up to
once per day
Once per day
or more
Age (y) 58 6 11
1
59 6 11 58 6 10 58 6 10 58 6 10 59 6 10 58 6 10 58 6 10
BMI (kg/m
2
)246 3256 5266 5286 6266 5266 5266 5266 6
Current smoker (%) 22 15 12 13 16 13 15 23
Family history of early coronary artery disease (%) 17 18 19 21 19 18 19 19
History of high blood pressure (%) 30 33 37 42 34 35 36 39
History of high cholesterol (%) 30 39 41 42 35 40 40 39
Weight change before onset of follow-up, 1976–1980 (kg) 0.75 6 3.7 0.88 6 3.9 1.02 6 4.1 1.11 6 4.8 0.80 6 4.2 0.88 6 3.8 1.06 6 4.1 1.27 6 4.6
Physical activity (METs
2
/wk) 17 6 23 18 6 22 18 6 22 17 6 23 19 6 24 18 6 21 16 6 21 14 6 21
Aspirin use at least once per week (%) 27 31 32 31 30 30 31 27
Vitamin E use (%) 20 25 25 22 24 25 21 16
Current hormone use (%) 20 26 27 25 24 27 24 20
Dietary intake (servings/d)
Red meat 1.16 6 0.69 1.04 6 0.58 1.05 6 0.57 1.10 6 0.61 0.98 6 0.62 1.03 6 0.56 1.20 6 0.62 1.36 6 0.71
Poultry 0.27 6 0.19 0.30 6 0.17 0.33 6 0.19 0.36 6 0.22 0.33 6 0.21 0.32 6 0.18 0.30 6 0.19 0.29 6 0.20
Fish 0.19 6 0.15 0.22 6 0.16 0.25 6 0.18 0.27 6 0.20 0.26 6 0.20 0.24 6 0.17 0.21 6 0.15 0.18 6 0.15
Whole-fat dairy 1.56 6 1.32 1.29 6 1.03 1.21 6 0.96 1.23 6 1.01 1.18 6 1.05 1.28 6 1.03 1.47 6 1.15 1.67 6 1.37
Low-fat dairy 0.85 6 0.87 1.01 6 0.82 1.04 6 0.81 1.00 6 0.82 1.06 6 0.88 1.03 6 0.81 0.88 6
0.79 0.67 6 0.76
Nuts 0.14 6 0.24 0.13 6 0.19 0.13 6 0.18 0.13 6 0.21 0.14 6 0.24 0.13 6 0.19 0.13 6 0.19 0.13 6 0.20
Fruit and vegetables 4.53 6 2.19 4.78 6 2.07 4.85 6 2.04 4.79 6 2.15 4.89 6 2.19 4.84 6 2.08 4.60 6 2.06 4.10 6 2.08
Alcohol (g/d) 6.0 6 10.5 5.3 6 9.6 5.7 6 9.8 6.0 6 10.5 7.0 6 11.2 5.5 6 9.6 5.1 6 9.3 4.9 6 10.1
Energy intake (kcal/d) 1691 6 467 1673 6 432 1661 6 428 1662 6 452 1541 6 421 1658 6 412 1772 6 447 1907 6 496
Cereal fiber intake (g/d)
3
3.6 6 1.9 4.2 6 2.0 4.0 6 1.9 3.7 6 1.9 3.9 6 2.2 4.2 6 1.9 3.7 6 1.7 2.9 6 1.6
trans Fatty acid intake (g/d)
3
3.5 6 1.2 3.3 6 1.0 3.3 6 0.96 3.3 6 1.01 3.3 6 1.1 3.3 6 1.0 3.5 6 1.0 3.4 6 1.0
1
Values are means 6 SDs and are standardized to the age distribution of the study population.
2
METs, metabolic equivalent tasks.
3
Cereal fiber and trans fatty acid intakes were calorie-adjusted by the residual method.
SODA AND STROKE RISK 1193
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TABLE 2
Age-standardized characteristics of 43,371 men in Health Professionals Follow-Up Study, 1986–2008
Low-calorie soda consumption Sugar-sweetened soda consumption
None
None up to
once per
week
Once per
week up to
once per day
Once per day
or more None
None up to
once per
week
Once per week
up to once
per day
Once per
day or more
Age (y) 62 6 11
1
62 6 11 62 6 11 61 6 10 62 6 11 62 6 11 62 6 11 61 6 10
BMI (kg/m
2
)256 3256 3266 3276 4266 4266 3266 3266 4
Current smoker (%) 6 4 4 4 4 4 5 8
Family history of early coronary artery disease (%) 11 11 13 14 13 11 11 13
History of high blood pressure (%) 27 33 36 42 33 35 33 35
History of high cholesterol (%) 31 41 43 45 36 42 39 39
Gain of .5 lb (2.27 kg) before onset of follow-up,
1981–1986 (%)
30 31 34 40 31 32 34 37
Physical activity (METs
2
/wk) 33 6 40 36 6 40 36 6 40 36 6 42 35 6 41 36 6 40 34 6 40 33 6 41
Aspirin use at least once per week (%) 30 37 38 39 33 38 36 33
Vitamin E use (%) 18 21 20 19 21 21 18 14
Dietary intake (servings/d)
Red meat 1.28 6 0.98 1.12 6 0.79 1.15 6 0.82 1.23 6 0.88 1.00 6 0.85 1.08 6 0.77 1.35 6 0.88 1.73 6 1.11
Poultry 0.36 6 0.26 0.40 6 0.24 0.42 6 0.26 0.47 6 0.30 0.41 6 0.28 0.41 6 0.25 0.41 6 0.26 0.41 6 0.30
Fish 0.30 6 0.26 0.31 6 0.24 0.34 6 0.26 0.37 6 0.29 0.37 6 0.29 0.32 6 0.244 0.31 6 0.25 0.28 6 0.25
Whole-fat dairy 1.39 6 1.38 1.17 6 1.08 1.08 6 0.99 1.12 6 0.99 1.02 6 1.08 1.13 6 1.05 1.33 6 1.19 1.59 6 1.35
Low-fat dairy 1.13 6 1.23 1.25 6 1.13 1.18 6 1.08 1.15 6 1.09 1.16 6 1.16 1.20 6 1.06 1.18 6
1.16 1.05 6 1.23
Nuts 0.25 6 0.37 0.25 6 0.33 0.24 6 0.33 0.26 6 0.37 0.25 6 0.38 0.24 6 0.33 0.25 6 0.33 0.26 6 0.35
Fruit and vegetables 5.46 6 2.74 5.52 6 2.63 5.52 6 2.59 5.56 6 2.73 5.76 6 2.81 5.56 6 2.63 5.38 6 2.56 4.90 6 2.60
Alcohol (g/d) 11.5 6 15.6 10.9 6 14.4 11.8 6 14.8 11.6 6 15.7 12.4 6 16.0 11.8 6 15.0 10.8 6 14.3 10.0 6 15.3
Energy intake (kcal/d) 2027 6 580 1989 6 546 1942 6 543 1982 6 568 1814 6 519 1919 6 509 2090 6 555 2396 6 616
Cereal fiber intake (g/d)
3
6.1 6 3.4 6.7 6 3.3 6.6 6 3.4 6.4 6 3.6 7.0 6 4.1 6.9 6 3.3 6.0 6 2.9 4.8 6 2.3
trans Fatty acid intake (g/d)
3
2.9 6 1.2 3.0 6 1.1 3.0 6 1.1 3.0 6 1.1 2.7 6 1.2 3.0 6 1.1 3.1 6 1.1 3.1 6 1.0
1
Values are means 6 SDs and are standardized to the age distribution of the study population.
2
METs, metabolic equivalent tasks.
3
Cereal fiber and trans fatty acid intakes were calorie-adjusted by the residual method.
1194 BERNSTEIN ET AL
Page 5
2 study populations were not significant. Adjustment for BMI, en-
ergy intake, and weight change before the begin ning of cohort fol-
low-up slightly attenuated the associations between lo w-calorie soda
consumption and stroke risk in men, but did not materially change
the associations in women or with sugar-sweetened bev erages.
Soda intake and ischemic and hemorrhagic stroke
In women, greater consumption of sugar-sweetened soda was
associated with a higher risk of ischemic stroke (RR per 1
serving/d: 1.19; 95% CI: 1.01, 1.39), whereas greater con-
sumption of low-calorie soda was associated with a greater risk
of hemorrhagic stroke (RR per 1 serving/d: 1.31; 95% CI:
1.15, 1.51) (Table 4). There were only 8 cases of hemorrhagic
stroke among men with a cumulative average intake of sug ar-
sweetenedsodaofonceperdayormore(Table4).Theasso-
ciation between low-calorie soda and hemorrhagic stroke risk
remained wh en results for men and women were pooled
(RR per 1 serving/d: 1.27; 95% CI: 1.12, 1. 43). Given the
potential for unstable estimates from the few cases in men,
TABLE 3
RRs (and 95% CIs) for stroke associated with soda consumption among 43,371 men in the Health Professionals Follow-Up Study and 84,085 women in the
Nurses’ Health Study
1
Servings
None
None up to once
per week
Once per week up to
once per day
Once per day
or more P-trend
2
RR for 1 serving/d
Sugar-sweetened soda
Men
Cases 464 381 499 72
Person-years 259,630 204,418 323,569 54,153
Age-adjusted 1.00 0.94 (0.82, 1.09) 1.02 (0.89, 1.16) 1.18 (0.92, 1.53) 0.11 1.16 (0.97, 1.40)
Multivariate
3
1.00 0.93 (0.80, 1.07) 0.99 (0.86, 1.13) 1.07 (0.82, 1.40) 0.43 1.08 (0.89, 1.31)
Multivariate
4
1.00 0.93 (0.80, 1.08) 0.99 (0.86, 1.14) 1.08 (0.82, 1.41) 0.43 1.08 (0.89, 1.32)
Women
Cases 918 950 896 174
Person-years 717,209 632,223 693,974 144,825
Age-adjusted 1.00 0.99 (0.90, 1.09) 1.17 (1.07, 1.29) 1.47 (1.25, 1.74) ,0.0001 1.34 (1.21, 1.49)
Multivariate
3
1.00 1.00 (0.91, 1.11) 1.12 (1.02, 1.24) 1.25 (1.05, 1.48) 0.004 1.17 (1.05, 1.30)
Multivariate
4
1.00 1.00 (0.91, 1.10) 1.11 (1.00, 1.22) 1.19 (1.00, 1.42) 0.02 1.14 (1.02, 1.27)
Pooled
5
Multivariate
4
1.00 0.98 (0.90, 1.06) 1.07 (0.98, 1.16) 1.16 (1.00, 1.34) 0.02 1.12 (1.02, 1.24)
Low-calorie soda
Men
Cases 459 246 509 202
Person-years 271,527 130,815 294,173 145,255
Age-adjusted 1.00 0.90 (0.77, 1.06) 1.02 (0.89, 1.16) 1.14 (0.96, 1.35) 0.04 1.11 (1.00, 1.23)
Multivariate
3
1.00 0.93 (0.79, 1.10) 1.05 (0.92, 1.20) 1.16 (0.97, 1.38) 0.03 1.12 (1.01, 1.24)
Multivariate
4
1.00 0.93 (0.79, 1.09) 1.03 (0.90, 1.18) 1.10 (0.92, 1.32) 0.13 1.09 (0.98, 1.21)
Multivariate
6
1.00 0.92 (0.78, 1.09) 1.02 (0.89, 1.17) 1.08 (0.91, 1.30) 0.18 1.07 (0.97, 1.19)
Women
Cases 797 504 1069 568
Person-years 655,418 328,868 758,680 445,264
Age-adjusted 1.00 0.91 (0.81, 1.02) 1.01 (0.91, 1.11) 1.15 (1.03, 1.28) ,0.001 1.11 (1.04, 1.17)
Multivariate
3
1.00 1.00 (0.89, 1.12) 1.11 (1.01, 1.23) 1.21 (1.08, 1.35) ,0.001 1.11 (1.04, 1.18)
Multivariate
4
1.00 1.00 (0.89, 1.12) 1.10 (1.00, 1.22) 1.18 (1.05, 1.33) 0.003 1.10 (1.03, 1.17)
Multivariate
6
1.00 1.00 (0.89, 1.12) 1.09 (0.99, 1.21) 1.17 (1.04, 1.31) 0.007 1.09 (1.02, 1.16)
Pooled
5
Multivariate
4
1.00 0.97 (0.88, 1.07) 1.08 (0.99, 1.17) 1.16 (1.05,1.28) ,0.0001 1.09 (1.04,1.15)
1
The Cox proportional hazards multivariate regression model is stratified on age (mo) and calendar time (11 time periods for the Health Professionals
Follow-up Study; 13 for the Nurses’ Health Study) and includes intakes of red meat, poultry, fish, nuts, whole- and low-fat dairy products, and fruit and vegetables
(all in quintiles of servings/d); cereal fiber (quintiles of g/d); alcohol intake (quintiles of g/d); trans fat intake (quintiles of g/d); cigarette smoking [never, past, or
current (1–14, 15–24, or 25 cigarettes/d)]; parental history of early myocardial infarction (before age 60 y); multivitamin use (quintiles of years); aspirin use at
least once per week (yes or no); vitamin E supplement use (yes or no); menopausal status in women (premenopausal, postmenopausal with no history of horm one
replacement, postmenopausal with a history of hormone replacement, or postmenopausal with current hormone replacement); and physical exercise (,3, 3 to ,9,
9to,18, 18 to ,27, or 27 metabolic equivalent tasks/wk); both sugar-sweetened and low-calorie sodas are included in the model.
2
Calculated by assigning median values to each quartile and treating them as a continuous variable.
3
Multivariate model without adjustment for BMI or energy intake.
4
Multivariate model with BMI (10 categories) and energy intake (quintiles of kcal/d).
5
Results from the multivariate model
4
were combined with the use of a fixed-effects model.
6
Multivariate model with BMI and energy intake and weight change before 1986 (pounds gained or lost during 5 y before 1986 in men or 4 y before
1980 in women).
SODA AND STROKE RISK 1195
Page 6
we did not evaluate the relation b etween soda intake and
subarachnoid hemorrhage in men. In women, when we fit
a m ultivariate model including BMI and energy intake, we
observed that a greater intake of low-calorie soda was asso-
ciated with a significantly higher risk of subarachnoid hem-
orrhage (RR per 1 serving/d: 1.37; 95% CI: 1.1 3, 1.65),
whereas sugar-sweetened soda was not (RR per 1 serving/d:
0.89; 95% CI: 0.62, 1.89).
Risk modification by diabetes and hypertension
Controlling for hypertension and diabetes durin g follow-up
in multivariate models each attenuated o ur r esults. The a sso-
ciations were further attenuated when c ontrolled for both: the
RRs of stroke in women across quartiles of suga r-sweetened
soda intake were 1.00, 1.00 , 1.09, and 1.14 (P-trend = 0.08) and
across quartiles of low-calorie so da intake were 1.00, 0.99,
1.06, and 1.11 (P-trend = 0.07); the RRs in men across quar-
tiles of sugar-sweetened soda intake were 1.00, 0.93, 0.99, and
1.05 (P-trend = 0.52) and across quartiles of low-calorie soda
intake were 1.00, 0.91, 0.99, a nd 1.03 ( P-trend = 0 .42) (see
supplementary Table 1 under “Supplemental data” in the on-
line issue). We did not observe a significant interaction be-
tween sugar-sweetened or low-calorie soda intake and a history
of either diabe tes or hypertension (see suppleme ntary Tables 2
and 3 unde r “Supplemental data” in the o nline issue).
Substitution of alternative beverages for soda with stroke
risk
Compared with 1 serving of sugar-sweetened or low-calorie
soda per day, 1 serving of either caffeinated or decaffeinated
coffee per day was associated with a significantly lower risk of
stroke (Figure 1, A and B). When compared with 1 serving
sugar-sweetened soda/d, 1 serving decaffeinated coffee/d was
associated with a 10% (95% CI: 1%, 19%) lower risk of stroke
and 1 serving caffeinated coffee/d with a 9% (95% CI: 0%,
17%) lower risk. When compared with 1 serving low-calorie
soda/d, 1 serving decaffeinated coffee/d was associated with
a 13% (7%, 18%) lower risk of stroke and 1 serving caffeinated
coffee/d with an 11% (95% CI: 7%, 16%) lower risk. Skim milk
was associated with an 11% (95% CI: 5%, 16%) lower risk
when substituted for low-calorie soda. When substituted for
TABLE 4
RRs (and 95% CIs) for ischemic and hemorrhagic stroke associated with soda consumption among 43,371 men in the Health Professionals Follow-Up Study
and 84,085 women in the Nurses’ Health Study
1
Servings
None
None up to once
per week
Once per week up to once
per day
Once per day
or more P-trend
2
RR for 1 serving/d
Sugar-sweetened soda
Ischemic stroke
Men 1.00 0.90 (0.75, 1.08) 0.89 (0.74, 1.06) 1.02 (0.72, 1.45) 0.98 1.00 (0.77, 1.30)
Women 1.00 1.05 (0.92, 1.20) 1.18 (1.02, 1.35) 1.28 (0.99, 1.65) 0.04 1.19 (1.01, 1.39)
Pooled
3
1.00 1.00 (0.89, 1.11) 1.06 (0.95, 1.18) 1.19 (0.97, 1.46) 0.07 1.13 (0.99, 1.30)
Hemorrhagic stroke
Men 1.00 0.75 (0.51, 1.11) 1.21 (0.86, 1.71) 0.82 (0.38, 1.77) 0.72 1.10 (0.66, 0.1.81)
Women 1.00 0.95 (0.75, 1.19) 1.00 (0.79, 1.26) 0.85 (0.56, 1.29) 0.54 0.92 (0.71, 1.20)
Pooled
3
1.00 0.90 (0.73, 1.09) 1.06 (0.88, 1.29) 0.85 (0.59, 1.22) 0.71 0.96 (0.76, 1.21)
Low-calorie soda
Ischemic stroke
Men 1.00 0.95 (0.77, 1.17) 0.98 (0.82, 1.17) 1.10 (0.87, 1.38) 0.24 1.08 (0.95, 1.24)
Women 1.00 1.05 (0.90, 1.23) 1.08 (0.94, 1.24) 1.15 (0.97, 1.35) 0.17 1.06 (0.97, 1.16)
Pooled
3
1.00 1.01 (0.89, 1.15) 1.04 (0.93, 1.16) 1.13 (0.99, 1.29) 0.07 1.07 (0.99, 1.15)
Hemorrhagic stroke
Men 1.00 0.77 (0.50, 1.20) 1.00 (0.72, 1.41) 1.05 (0.66, 1.67) 0.57 1.08 (0.82, 1.43)
Women 1.00 0.96 (0.72, 1.28) 1.08 (0.85, 1.37) 1.55 (1.20, 2.00) ,0.0001 1.31 (1.15, 1.51)
Pooled
3
1.00 0.90 (0.71, 1.15) 1.06 (0.87, 1.28) 1.42 (1.14, 1.77) ,0.001 1.27 (1.12, 1.43)
1
The Cox proportional hazards multivariate regression model is stratified on age (mo) and calendar time (11 time periods for the Health Professionals
Follow-up Study; 13 for the Nurses’ Health Study) and includes intakes of red meat, poultry, fish, nuts, whole- and low-fat dairy products, and fruit and
vegetables (all in quintiles of servings/d); cereal fiber (quintiles of g/d); alcohol intake (quintiles of g/d); trans fat intake (quintiles of g/d); cigarette smoking
[never, past, or current (1–14, 15–24, or 25 cigarettes/d)]; parental history of early myocardial infarction (before age 60 y); multivitamin use (quintiles of
years); aspirin use at least once per week (yes or no); vitamin E supplement use (yes or no); menopausal status in women (premenopausal, postmenopausal
with no history of hormone replacement, postmenopausal with a history of hormone replacement, or postmenopausal with current hormone replacement);
physical exercise (,3, 3 to ,9, 9 to ,18, 18 to ,27, or 27 metabolic equivalent tasks/wk); and BMI (10 categories) and energy intake (quintiles of kcal);
both sugar-sweetened and low-calorie sodas are included in the model. Number of cases of hemorrhagic stroke across quartiles of sugar-sweetened soda: 71,
46, 92, and 8 in men and 181, 152, 156, and 30 in women. Number of cases of ischemic stroke across quartiles of sugar-sweetened soda: 288, 231, 281, and 43
in men and 462, 508, 463, and 80 in women. Number of cases of hemorrhagic stroke across quartiles of low-calorie soda: 78, 31, 80, and 28 in men and 158,
75, 162, and 124 in women. Number of cases of ischemic stroke across quartiles of low-calorie soda: 272, 150, 292, and 129 in men and 387, 283, 562, and
281 in women.
2
Calculated by assigning median values to each quartile and treating them as a continuous variable.
3
Results from the multivariate model without adjustment for BMI or energy intake were combined with the use of a fixed-effects model.
1196 BERNSTEIN ET AL
Page 7
sugar-sweetened or low-calorie soda, tea and orange juice were
associated with a trend toward reduced risk.
DISCUSSION
In these large prospective cohort studies of men and women,
we observed that a higher consumption of sugar-sweetened and
low-calorie sodas was associated with a higher risk of stroke. The
risks appeared higher in women than in men. The associations
were independent of established dietary and nondietary cardio-
vascular disease risk factors, including BMI and energy intake.
Multiple mechanisms may explain these findings. In sugar-
sweetened sodas, the sugar load may lead to rapid increases in
blood glucose and insulin, which over time lead to glucose in-
tolerance, insulin resistance, and inflammation; these physiologic
changes in turn influence atherosclerosis, plaque stability, and
thrombosis—a risk factor for ischemic stroke (3). Fructose can be
converted to visceral and hepatic fat (30) and enhances lipo-
genesis and triglyceride synthesis (31). Fructose can also increase
serum uric acid, which can reduce endothelial nitric oxide and
increase blood pressure—a risk factor for ischemic and hem-
orrhagic stroke (32). Because intake of sugar-sweetened bever-
ages is not regulated by the body in the same manner as foods,
their consumption may lead to excess caloric intake (33);
however, this mechanism is unlikely to explain our findings
because control for energy intake in our models did not alter our
results. The caramel coloring in sugar-sweetened and low-calorie
colas has advanced-glycation end products, which have been
linked with inflammation, and which in turn has been linked with
the initiation, growth, and destabilization of atherosclerotic le-
sions (3, 26). Whereas an inverse U-shaped association has been
reported between caffeine intake and incident hypertension,
a linear association has been reported between increasing soda
intake and hypertension, which suggests that constituents in soda
other than caffeine affect blood pressure (34).
In comparison with soda, coffee contains chlorogenic acids,
lignans, and magnesium, which act as antioxidants and mediators
of glucose metabolism and may reduce stroke risk (35). Higher
intakes of potassium, magnesium, and calcium have been as-
sociated with a reduced stroke risk (36): one or more of these
nutrients may help explain the reduction in risk seen when skim
milk or orange juice is substituted for soda. Although a modest
benefit with substitution of water for soda cannot be excluded
because the CI for the substitution includes a modest benefit, the
significant substitutions for soda were with beverages that appear
to have inherently positive benefits for stroke reduction.
We did not observe a strong association between a diagnosis of
hypertension or diabetes and a subsequent change in soda intake.
We also did not find a significant interaction between soda intake
and hypertension or diabetes. However, when we controlled for
these diagnoses in our multivariate model, the strength of the
associations between both sugar-sweetened and low-calorie soda
intakes and stroke risk was attenuated. These findings suggest
that hypertension and diabetes may be intermediates, rather than
confounders or effect-modifiers, of the soda-stroke association.
Our work builds on previous research on the relation between
sugar-sweetened beverages and incident chronic disease. Other
studies have evaluated the relation between soda consumption
and metabolic disorders (3, 4, 9, 37–39), yet few have examined
soda consumption and incident cardiovascular disease (6, 40, 41).
A case-crossover study with only 209 men and 181 women
reported no increase in stroke risk in the hour after cola con-
sumption (RR: 1.0; 95% CI: 0.4, 2.4; P = 0.95) (40), and intake
was not associated with total mortality or cardiovascular mortality
among 1900 men and women followed for an average of 3.8 y
after an acute myocardial infarction (41). Of the sugar-sweetened
beverages, cola was recently reported to be associated with the
FIGURE 1. Pooled RRs and 95% CIs associated with substitution of alternative beverages for sugar-sweetened soda (A) and low-calorie soda (B) among
43,371 men and 84,085 women (1 serving/d). RRs and variances for each substitution from each cohort were derived from a Cox proportional hazards
multivariate model and then pooled in a fixed-effects model to arrive at a summary estimate of the effect of substituting one beverage for another in relation to
total stroke risk; the Q statistic P value for between-study heterogeneity (null hypothesis is that there is no heterogeneity between Health Professionals Follow-
Up Study and Nurses’ Health Study) for estimate of effect of substitutions is .0.05.
SODA AND STROKE RISK 1197
Page 8
greatest risk of CAD (RR per a 2-serving/d increase: 1.35; 95%
CI: 1.15, 1.57) (6), whereas low-calorie beverages were not as-
sociated with risk (6).
Our analysis had strengths and limitations. The prospective
collection of data on soda consumption and lifestyle factors
minimized the potential for recall bias or reverse causation. The
high rate of follow-up reduced bias due to loss to follow-up.
Repeated dietary intake data served to reduce random mea-
surement error, and any residual random error would likely lead
to an underestimate of the true effect of exposures with outcome.
The ability to measure for known cardiovascular disease risk
factors permitted control for possible confounders in multivar-
iable models. Adjustment for the presence of behaviors, such as
regular exercise and taking a daily multivitamin, reduces the
likelihood that lifestyle characteristics confound the associations
observed between substituting alternative beverages for soda.
Nevertheless, because of the observational nature of this study,
we cannot exclude the possibility of residual and unmeasured
confounding. Our nding of an association between low-calorie
soda intake and stroke risk should be interpreted with caution,
because we previously did not nd an association between low-
calorie beverages and weight gain (42), diabetes (9), or CAD (6),
and there is not a clear biologic mechanism between low-calorie
soda consumption and incident stroke. Finally, there were few
cases of hemorrhagic stroke among men, especially among men
consuming 1 sugar-sweetened soda/d; therefore, our analysis
of the association between sugar-sweetened soda consumption
and hemorrhagic stroke among men must also be interpreted
cautiously.
In conclusion, in these large studies of US men and women, we
found that greater consumption of sugar-sweetened and low-
calorie sodas was associated with a higher risk of stroke.
Compared with the same number of servings of soda, con-
sumption of caffeinated or decaffeinated coffee was associated
with a lower risk. Stroke burden may therefore be reduced by
changing patterns of beverage consumption in the United States.
The authors’ responsibilities were as follows—AMB and WCW: designed
the research; AMB, LdK, AJF, AJF, KMR, and WCW: analyzed the data and
wrote the manuscript; and AMB: conducted the research and had primary
responsibility for the final content. All authors read and approved the final
manuscript. None of the authors declared a conflict of interest. Neither the
NIH nor the Harvard Human Nutrition Program had a role in the design
or conduct of the study; collection, management, analysis, or interpretation
of the data; or preparation, review, or approval of the manuscript.
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    • "American adult men in the top quartile of SSB intake have been found to have a 24% higher risk of type 2 diabetes [2] and a 20% higher risk of coronary heart disease [3] relative to those in the bottom quartile. Furthermore, compared with individuals who did not consume SSBs, those who consumed one or more servings per day had a 16% higher risk of any stroke [4]. In European adults, one 12-ounce daily increment in SSB intake was associated with a 22% increase in the risk of type 2 diabetes [5]. "
    [Show abstract] [Hide abstract] ABSTRACT: To examine the association between sugar-sweetened beverage consumption and metabolic syndrome risk factors in Korean adults. We used data from 13,972 participants (5432 men and 8540 women) aged ≥30years, from the 2007-2011 Korea National Health and Nutrition Examination Survey. The subjects were divided into six groups based on their soft drink consumption levels from a food frequency questionnaire. Dietary sugar intake was compared among groups using 24-hour dietary recall data. The highest soft drink consumption frequency category was ≥4 times per week, observed in 4.6% of men and 1.7% of women. The percentage of energy from total sugar and sugar in processed foods increased with increased soft drink consumption in both men and women. In the highest consumption group, the percentage of energy from sugar in processed foods was 8.9% in men and 11.0% in women. After adjusting for potential confounding variables, greater consumption of soft drinks was positively associated with all of the components of metabolic syndrome, except the high density lipoprotein (HDL) cholesterol level, in women only. Women who consumed soft drinks ≥4 times per week had a 74% higher risk of metabolic syndrome compared to those who consumed soft drinks infrequently (OR: 1.74; 95% CI: 1.00-3.03; P for trend <0.0001). High levels of soft drink consumption might constitute an important determinant of metabolic syndrome and its components only in Korean adult women. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Jul 2015 · Metabolism: clinical and experimental
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    • "Some epidemiologic studies have shown a positive correlation between the consumption of these drinks and the incidence of cardiovascular disease (CVD) and stroke [10][12], while other reports have demonstrated that the intake of green tea and coffee reduces the risk and mortality of CVD in Japan [13][15] . Carbonated beverages, or sodas, have frequently been demonstrated to increase the risk of metabolic syndrome and CVD, such as subclinical cardiac remodeling and stroke [16] [17]. The Fire and Disaster Management Agency of Japan launched a prospective, nationwide, population-based, cohort study in subjects who had an OHCA to evaluate the effect of the nationwide dissemination of public-access Automated External Defibrillators (AEDs) on the rate of survival among patients who had an OHCA, and the Japanese Circulation Society (JCS) Resuscitation Science Study (JCS-ReSS) Group had a suitable database in January 2005 [18]. "
    Full-text · Article · Jan 2015 · World Journal of Cardiovascular Diseases
    • "In this study, the authors say that participants who left excessive items blank on their baseline food-frequency questionnaire and those who reported implausibly lowor high-energy intakes were excluded. In addition, they included only low-energy cola with caffeine (eg, Diet Coke and Tab with caffeine), low-energy cola without caffeine (eg, Pepsi Free), other low-energy carbonated beverages (eg, Diet 7Up, Fresca, Diet Mountain Dew, and diet ginger ale), sugar-sweetened cola with caffeine (eg, Coke and Pepsi), sugar-sweetened cola without caffeine (eg, caffeine-free Coke and caffeine-free Pepsi), and other carbonated beverages with sugar (eg, 7Up, Mountain Dew, Surge, and Dr Pepper) [5]. But they did not include energy drinks. "
    No preview · Article · Dec 2014 · American Journal of Emergency Medicine
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