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Diet Drink Consumption and the Risk of Cardiovascular Events: A Report from the Women’s Health Initiative

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Background: Data are limited regarding the influence of diet drink consumption on cardiovascular disease (CVD) outcomes. Objective: We aimed to evaluate the relationship between diet drink intake and cardiovascular events. Design: We conducted a retrospective cohort study, utilizing data from the national, multicenter Women's Health Initiative Observational Study (WHI OS), recruiting subjects from 1993 to 1998. Patients: Post-menopausal women with available diet drink intake data, without pre-existing CVD and who survived ≥ 60 days were included in the study. Main meaures: A composite of incident coronary heart disease, heart failure, myocardial infarction, coronary revascularization procedure, ischemic stroke, peripheral arterial disease and CVD death was used as the primary outcome. CVD death and all-cause mortality were secondary outcomes. Adjusted Cox proportional hazards models were used to compare primary and secondary outcomes across diet drink intake strata. Key results: In all, 59,614 women, mean age 62.8 years, were included for analysis. In unadjusted analysis over a follow-up of 8.7 ± 2.7 years, the primary outcome occurred in 8.5 % of the women consuming ≥ 2 diet drinks/day, compared to 6.9 %, 6.8 % and 7.2 % in the 5-7/week, 1-4/week and 0-3/month groups, respectively. After controlling for other CVD risk factors, women who consumed ≥ 2 drinks/day had a higher adjusted risk of CVD events (HR 1.3, 95 % CI 1.1-1.5), CVD mortality (HR 1.5, 95 % CI 1.03-2.3) and overall mortality (HR 1.3, 95 % CI 1.04-1.5) compared to the reference group (0-3 drinks/month). Conclusions: This analysis demonstrates an association between high diet drink intake and CVD outcomes and mortality in post-menopausal women in the WHI OS.
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Diet Drink Consumption and the Risk of Cardiovascular Events:
A Report from the Womens Health Initiative
Ankur Vyas, MD
1
, Linda Rubenstein, PhD
2
, Jennifer Robinson, MD, MPH
1,2
,
Rebecca A. Seguin, PhD, CSCS
3
, Mara Z. Vitolins, DrPH, MPH, RD
4
,
Rasa Kazlauskaite, MD, MSc, FACE
5,6
, James M. Shikany, DrPH
7
, Karen C. Johnson, MD, MPH
8
,
Linda Snetselaar, RD, PhD
2
, and Robert Wallace, MD, MSc
2,9
1
Division of Cardiovascular Medicine, University of Iowa Hospitals & Clinics, Iowa City, IA, USA;
2
Department of Epidemiology, College of Public Health,
University of Iowa, Iowa City, IA, USA;
3
Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA;
4
Department of Epidemiology & Prevention, Wake
Forest School of Medicine, Winston-Salem, NC, USA;
5
Department of Preventive Medicine, Rush University, Chicago, IL, USA;
6
Department of Internal
Medicine, Rush University, Chicago, IL, USA;
7
Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, USA;
8
Department of
Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA;
9
Department of Internal Medicine, University of Iowa Hospitals and
Clinics, Iowa City, IA, USA.
BACKGROUND: Data are limited regarding the influence
of diet drink consumption on cardiovascular disease
(CVD) outcomes.
OBJECTIVE: We aimed to evaluate the relationship be-
tween diet drink intake and cardiovascular events.
DESIGN: We conducted a retrospective cohort study, uti-
lizing data from the national, multicenter Womens Health
Initiative Observational Study (WHI OS), recruiting sub-
jects from 1993 to 1998.
PATIEN T S: Post-menopausal women with available diet
drink intake data, without pre-existing CVD and who
survived 60 days were included in the study.
MAIN MEAURES: A composite of incident coronary heart
disease, heart failure, myocardial infarction, coronary re-
vascularization procedure, ischemic stroke, peripheral
arterial disease and CVD death was used as the primary
outcome. CVD death and all-cause mortality were sec-
ondary outcomes. Adjusted Cox proportional hazards
models were used to compare primary and secondary
outcomes across diet drink intake strata.
KEY RESULTS: In all, 59,614 women, mean age
62.8 years, were included for analysis. In unadjusted
analysis over a follow-up of 8.7±2.7 years, the primary
outcome occurred in 8.5 % of the women consuming 2
diet drinks/day, compared to 6.9 %, 6.8 % and 7.2 % in
the 57/week, 14/week and 03/month groups, respec-
tively. After controlling for other CVD risk factors, women
who consumed 2 drinks/day had a higher adjusted risk
of CVD events (HR 1.3, 95 % CI 1.11.5), CVD mortality
(HR 1.5, 95 % CI 1.032.3) and overall mortality (HR 1.3,
95 % CI 1.041.5) compared to the reference group (03
drinks/month).
CONCLUSIONS: This analysis demonstrates an associa-
tion between high diet drink intake and CVD outcomes
and mortality in post-menopausal women in the WHI OS.
KEY WORDS: diet; cardiovascular diseases; lifestyle; diet drinks; artificial
sweeteners.
J Gen Intern Med
DOI: 10.1007/s11606-014-3098-0
© Society of General Internal Medicine 2014
INTRODUCTION
Observational studies have demonstrated an association be-
tween sugar-sweetened beverages and obesity, metabolic syn-
drome, and cardiovascular disease (CVD) outcomes; this as-
sociation is attributed to increased energy and sugar load.
15
Diet drinks are often consumed as a low-calorie alternative to
sugar-sweetened drinks, and one out of every five Americans
drinks diet soda every day.
6
Several population-based studies
have demonstrated a positive association between diet drinks
and the metabolic syndrome, which in turn is associated with
increased risk for CVD.
2,79
However, data are limited as to
whether there is an increased CVD risk associated with diet
drink consumption. Given the large population directly affect-
ed by such an association, this study was performed to eval-
uate the effect of diet drink consumption on CVD outcomes in
the Womens Health Initiative Observational Study (WHI OS)
cohort.
METHODS
The WHI is a multicenter national study that involved 40
centers across 24 states and the District of Columbia and
included 161,808 postmenopausal women.
10,11
It consisted
of three overlapping Clinical Trials (CT) including 68,133
women, as well as an Observational Study (OS) enrolling
93,676 subjects. Recruitment to the WHI took place from
1993 to 1998, and enrolled postmenopausal women between
50 and 79 years of age.
11
The OS cohort was derived from the
women who were screened for the clinical trials but were
ineligible or unwilling to be randomized, as well as from those
Electronic supplementary material The online version of this article
(doi:10.1007/s11606-014-3098-0) contains supplementary material,
which is available to authorized users.
Received April 21, 2014
Revised August 11, 2014
Accepted October 27, 2014
who responded to a direct invitation to be screened for the
OS.
12
Exclusion criteria (for both the CT and the OS) were the
presence of any medical condition with a predicted survival of
< 3 years, concerns about adherence, and active participation
in other randomized trials. An effort was made to enroll
women of racial and ethnic minority groups, with a target of
20 % of overall enrollment.
13
No significant sampling issues
were noted with regards to participant enrollment. All partic-
ipants provided written informed consent, and the study pro-
tocol was approved by institutional review boards of all par-
ticipating centers.
The OS cohort was used for analysis for this study. After
baseline evaluation at a clinic visit, updates regarding medical
histories and selected exposure data were obtained annually by
mailed questionnaire. All participants were also invited to a
clinic follow-up visit at 3 years after enrollment.
13
Dietary
information was collected using food frequency question-
naires obtained at baseline and follow-up clinic visits.
14
The
questionnaire at follow-up year 3 also included information
regarding diet drink consumption over the previous 3 months.
Diet drink intake was categorized into nine groups on the
questionnaire, ranging from none or less than one per month
to more than six drinks per day, with each drink defined as the
equivalent of a 12-oz can of beverage. Follow-up ended in
2005, and ranged from six to ten years, depending on year of
enrollment.
Inclusion and Exclusion Criteria
All women in the OS for whom diet drink intake data was
available were included for analysis in this study. Exclusion
criteria were (1) presence of any of the following pre-existing
diagnoses: coronary heart disease (CHD), heart failure (HF),
myocardial infarction (MI), coronary revascularization proce-
dure, ischemic stroke, peripheral arterial disease (PAD) as well
as other related cardiovascular and thromboembolic events
(angina, carotid artery disease, hemorrhagic stroke, transient
ischemic attack, pulmonary embolism and deep vein throm-
bosis); or (2) a survival of less than 60 days after collection of
diet drink consumption data.
Outcomes
A composite of incident CHD, HF, MI, coronary revascular-
ization procedure, ischemic stroke, PAD and CVD death was
used as the primary outcome, with time to first occurrence of
any of these events being the relevant endpoint. Secondary
outcomes were rates of CVD death, as well as death from any
cause. Outcomes in the OS were identified through self-report
at annual contacts, and specific details were obtained as need-
ed using standardized questionnaires and request of medical
records.
15
Data linkage with the National Death Index was
performed to assure completeness of survival data, and causes
of death were actively investigated. Adjudication of outcomes
was performed by physicians at the Clinical Centers, the
Clinical Coordinating Center, and the National Institutes of
Health, using a staged approach. All primary and safety end-
points, as well as a sample of locally adjudicated secondary
endpoints, were reviewed centrally. The adjudicating physi-
cians were blinded to any participant information that could
potentially result in bias.
Statistical Analysis
Risk factors and demographic characteristics included base-
line self-reported age, race, education, income, body mass
index (BMI), smoking, alcohol intake, hormone therapy
(HT) use, physical activity, energy intake, salt intake, history
of diabetes,
16
hypertension, or high cholesterol, as well as
sugar-sweetened beverage intake. Age was assessed in years
as both continuous and categorical (4959, 6064, 6569,
70), physical activity was measured as total energy expended,
and energy intake was measured as calibrated total calories.
17
Unadjusted relationships between continuous baseline var-
iables were assessed using t-tests comparing least square
means from general linear models, and between categorical
variables using the Pearson chi-square test. Occurrence of a
CVD event, CVD death and all-cause mortality were mea-
sured in years from the date of Visit 3 until the first CVD
event, death or until the participant was last known to be alive.
Unadjusted differences in incidence of primary and secondary
outcomes across diet drink consumption strata were assessed
using the Pearson chi-square test. Cox proportional hazards
models were used to assess the relationship of diet soda intake
with occurrence of the first CVD event or time to death,
adjusting for CVD risk factors.
18
Hazard ratios (HR) and
95 % confidence intervals (CI) were calculated to measure
the magnitude of the associations. Four different models were
constructed. Model I was unadjusted; Model II was adjusted
for age, race, education and income; Model III was adjusted
for the variables in Model II plus smoking status, BMI, and a
history of diabetes, hypertension and hyperlipidemia; and
Model IV was adjusted for the variables in Model III plus
alcohol intake, log calibrated energy intake, physical activity,
sugar-sweetened beverage intake, salt intake, and HT. Subjects
with missing variables were excluded from analysis. All var-
iables were assessed for the proportional hazards assumption
before inclusion in the model. Adjusted cardiac event models
were stratified on hypertension and high cholesterol, and
adjusted mortality models were stratified on hypertension
and the history of diabetes, because these variables did not
meet the proportional hazards assumption.
Additional sensitivity and exploratory analyses were also
performed. In order to decrease the risk of reverse causality,
women with a history of diabetes, hypertension, and high
cholesterol were excluded and the adjusted risk (Model IV
above) for the primary outcome was calculated in the residual
healthier population. The impact of missing salt intake and
calibrated energy intake data was evaluated by constructing
fully adjusted models for the primary outcome after excluding
these variables. The effect of BMI on the relationship between
relationship of diet drink intake and outcomes was further
investigated by using interaction terms for BMI and diet drink
Vyas et al.: Diet Drinks and Cardiovascular Events JGIM
categories in the fully adjusted models. The role of diet quality
was assessed by including Healthy Eating Index-2005 (HEI-
2005) scores in the model (with salt and energy intake exclud-
ed to prevent double counting). HEI-2005 has previously been
used in the WHI and other population based cohorts, and has
been demonstrated to be associated with both cardiometabolic
risk factors and cardiovascular outcomes and mortality.
1923
Finally, as the definition of HF in the WHI was sub-optimal, a
revised primary outcome that excluded HF was constructed,
and adjusted hazard ratios were calculated for the revised
primary outcome as well as HF alone.
This manuscript was prepared in accordance with the
Strengthening the Reporting of Observational Studies in Epi-
demiology (STROBE) Statement.
24
All statistical significance
was based on two-tailed tests and p values 0.050. Statistical
analyses were performed using SAS 9.3 [SAS System for
Windows, version 9.3. Cary, NC: SAS Institute. 20022010].
RESULTS
Of 93,676 women who were part of the WHI OS, 59,614 met
criteria for this study and were included for analysis (Fig. 1).
Among non-deceased women who met other inclusion
criteria, 9,946 were excluded due to lack of diet drink data
secondary to either absent or partial year 3 follow-up. Those
who were excluded had a higher proportion of women older
than 70 years of age as well as women of African American or
Hispanic race, and had lower income and educational status,
compared to women who were included in the analysis.
Almost two-thirds of those included (38,337 women,
64.3 %) fell into the lowest consumption category (03 drinks
per month), and there were 11,590 (19.4 %), 6,702 (11.2 %)
and 2,985 (5.0 %) women who consumed 14 drinks per
week, 57 drinks per week, and two or more drinks per day,
respectively (Table 1). Categorization of diet drink intake was
constructed in accordance with previous studies and in order to
satisfy proportional hazard assumptions.
1,2,25
The mean fol-
low up was 8.7 (SD±2.7) years. The average age of the
included cohort was 62.8 (SD±7.2) years, and a majority of
women (85.7 %) were white.
Baseline variables differed significantly between the four
groups (Table 1). Women who consumed 2 diet drinks/day
were younger than the other groups, with a mean age of
59.5 years, compared to 63.5 years in the 03 drinks per month
group. There was increased prevalence of diabetes and hyper-
tension in the women who consumed the most diet drinks, and
they had a higher BMI, a greater proportion of smokers and
higher calibrated energy intake. When non-diet drink con-
sumption was assessed across the different diet drink intake
strata, no significant difference was found.
Outcomes
The composite primary outcome occurred in 8.5 % of the
women who consumed 2 diet drinks/day, compared to 6.9,
6.8 and 7.2 % of the women in the 57 drinks/week, 14
drinks/week and 03 drinks/month groups, respectively
(Table 2). Unadjusted incidence of the secondary out-
comes did not differ markedly between the 2diet
drinks/day and 03 diet drinks/month groups, with inci-
dence of CVD death and overall mortality being 1.6 and
7.8 %, respectively, in the highest consumption group, and
1.7 and 7.7 % in the lowest (Table 2).
Cox proportional hazard models demonstrated that women
who consumed 2 drinks/day had a higher unadjusted risk of
experiencing CVD events (in the form of the combined end-
point) as compared to those who consumed 03 drinks/month
(the reference group), with the difference being statistically
significant (Model I; N: 59,614; HR 1.2, 95 % CI 1.041.3)
(Table 3). This increased risk among the highest consumption
category persisted when the models were adjusted progres-
sively for baseline demographic variables (Model II; N:
55,073; HR 1.6, 95 % CI 1.41.9), common CVD risk factors
(Model III; N: 53,037; HR 1.3. 95 % CI 1.21.5), and other
possible confounders (Model IV; N: 33,619; HR 1.3, 95 % CI
1.11.5). No significant difference in risk was found between
the other consumption groups and the reference group, with
regards to the primary endpoint. There was progressive de-
crease in sample size with the Cox proportional hazard models
secondary to missing data, with Model IV especially limited
by missing values for energy and salt intake.
Unadjusted analysis (Model I) did not demonstrate a differ-
ence between the 2 drinks/day group and the 03 drinks/
month group with regards to either CVD death (N: 59,447; HR
0.9, 95 % CI 0.71.2) or overall mortality (N: 59,447; HR 1.0,
95 % CI 0.91.1) (Table 3). However, with adjustment for
baseline demographic characteristics, CVD risk factors and
other confounders, there emerged a significant risk of both
CVD death (Model II: N 55,073, HR 1.8, 95 % CI 1.32.4;
Model III: N 53,037, HR 1.4, 95 % CI 1.041.9; Model IV: N
33,619, HR 1.5, 95 % CI 1.032.3) and overall mortality
(Model II: N 55,073, HR 1.5, 95 % CI 1.31.7; Model III: N
53,037, HR 1.4, 95 % CI 1.21.6; Model IV: N 33,619, HR
1.3, 95 % CI 1.041.5) with consumption of 2 diet drinks/
day. Hazard ratios for adjustment covariates for both primary
and secondary outcomes are listed in the online appendix.
Figure 1 Selection of study cohort.
Vyas et al.: Diet Drinks and Cardiovascular EventsJGIM
Sensitivity and Exploratory Analyses
A history of diabetes, hypertension and high cholesterol was
absent in 38,658 women, and these were classified as being
healthier at baseline. The hazard ratios for the primary outcome
for these were similar to those for the primary analysis;
however, the 95 % confidence intervals were wider and did
not reach statistical significance (Table 4). Salt and calibrated
energy intake data were missing in 18,097 (30.4 %) women,
and this was uniformly distributed across the diet drink con-
sumption groups. Excluding salt and calibrated energy intake
from the model did not result in a significant change in the
Table 1. Baseline Characteristics of Women Included in Analysis
Characteristics Diet drink consumption
03/month 14/week 57/week 2/day p value*
N (%) 38,337 (64.3) 11,590 (19.4) 6,702 (11.2) 2,985 (5.0)
Age (Mean ± SD) 63.5±7.2 62.3±6.9 61.2±6.9 59.5±6.5 < 0.0001
Race (%) < 0.0001
American Indian 128 (0.3) 28 (0.2) 30 (0.4) 13 (0.4)
Asian/Pacific Islander 1,401 (3.7) 270 (2.3) 130 (1.9) 36 (1.2)
African American 2,559 (6.7) 720 (6.2) 387 (5.8) 207 (7.0)
Hispanic 1,282 (3.4) 363 (3.1) 207 (3.1) 98 (3.3)
White 32,418 (84.8) 10,068 (87.1) 5880 (88.0) 2601 (87.4)
Other 441 (1.2) 109 (0.9) 49 (0.7) 22 (0.7)
Education (%) < 0.0001
< High school, High school 10,498 (27.6) 3,426 (29.8) 1,936 (29.1) 893 (30.2)
Some college 9,905 (26.0) 3,009 (26.2) 1,808 (27.2) 838 (28.3)
College graduate, > College 17,656 (46.4) 5,069 (44.1) 2,899 (43.6) 1,228 (41.5)
Income in dollars (%) < 0.0001
< 35,000 12,759 (35.8) 3,631 (33.5) 1,902 (30.2) 925 (32.9)
35,000< 75,000 14,852 (41.7) 4,643 (42.9) 2,772 (44.0) 1,193 (42.4)
75,000 8,009 (22.5) 2,551 (23.6) 1,628 (25.8) 693 (24.7)
BMI (%) < 0.0001
<25kg/m
2
17,692 (46.5) 3,882 (33.7) 1,986 (29.9) 686 (23.2)
2530 kg/m
2
12,765 (33.6) 4,327 (37.6) 2,424 (36.5) 1,028 (34.7)
>30kg/m
2
7,572 (19.9) 3,301 (28.7) 2,234 (33.6) 1,245 (42.1)
Smokers (%) 1716 (4.5) 394 (3.4) 303 (4.5) 227 (7.7) < 0.0001
Alcohol intake (%) 0.086
< 0.5 drinks/week 22,086 (57.7) 6,812 (58.9) 3,875 (57.9) 1,769 (59.3)
0.52 drinks/week 5,821 (15.2) 1,684 (14.6) 1,001 (15.0) 467 (15.7)
> 2 drinks/week 10,352 (27.1) 3,077 (26.6) 1,812 (27.1) 745 (25.0)
HT users (%) < 0.0001
Never 12,548 (32.8) 3369 (29.1) 1896 (28.3) 878 (29.6)
Estrogen only 11,014 (28.8) 3623 (31.3) 2072 (31.0) 943 (31.7)
Either one or both 14,565 (38.1) 4541 (39.3) 2697 (40.3) 1136 (38.2)
Unknown 129 (0.3) 33 (0.3) 29 (0.4) 14 (0.5)
Physical activity (total energy expended, MET-hours/week, Mean ± SD) 12.0±13.4 12.1±13.4 11.6±13.0 11.9±13.2 0.38
Calibrated energy intake (kcal, Mean ± SD) 2033±187 2092±196 2130±209 2190±232 < 0.0001
Salt intake (mg, Mean ± SD) 2393±1077 2519±1098 2601±1193 2732±1388 < 0.0001
History of diabetes (%) 2636 (6.9) 1178 (10.2) 810 (12.1) 502 (16.8) < 0.0001
History of hypertension (%) 9962 (26.2) 3281 (28.5) 1956 (29.4) 927 (31.2) < 0.0001
History of high cholesterol (%) 4264 (11.4) 1512 (13.3) 844 (12.8) 384 (13.1) < 0.0001
Sugar-sweetened beverage intake 0.44
None or < 1/month 23,794 (62.1) 7,111 (61.4) 4,133 (61.7) 1,831 (61.3)
< Once a day 12,798 (33.4) 3,944 (34.0) 2,253 (33.6) 1,012 (33.9)
Daily 1,745 (4.6) 535 (4.6) 316 (4.7) 142 (4.8)
SD standard deviation, BMI body mass index, HT hormone therapy
*Unadjusted p value
Table 2. Incidence of Primary and Secondary Outcomes Across Diet Drink Consumption Strata
Outcomes Diet drink consumption
03/month 14/week 57/week 2/day p value*
Total subjects 38,337 11,590 6,702 2,985
Cardiovascular events (%)
Combined 2,745 (7.2) 785 (6.8) 462 (6.9) 254 (8.5) 0.010
CHD 1,030 (2.7) 279 (2.4) 159 (2.4) 94 (3.1) 0.055
HF 349 (0.9) 95 (0.8) 53 (0.8) 37 (1.2) 0.13
MI 819 (2.1) 219 (1.9) 122 (1.8) 74 (2.5) 0.065
Coronary revascularization 1,039 (2.7) 325 (2.8) 204 (3.0) 111 (3.7) 0.008
Stroke 652 (1.7) 192 (1.7) 94 (1.4) 58 (1.9) 0.212
PAD 160 (0.4) 49 (0.4) 27 (0.4) 22 (0.7) 0.079
Cardiac death 642 (1.7) 163 (1.4) 90 (1.3) 47 (1.6) 0.076
Mortality (%)
All cause death 2,970 (7.7) 789 (6.8) 445 (6.6) 233 (7.8) 0.003
CHD coronary heart disease, HF heart failure, MI myocardial infarction, PAD peripheral arterial disease
*Unadjusted p values (χ
2
test)
Vyas et al.: Diet Drinks and Cardiovascular Events JGIM
hazard ratios for the primary outcome (HR for 2 diet drink/
daygroup:1.3;95%CI1.11.5). Addition of the HEI-2005
score in the model also did not lead to any notable change in the
association between diet drink consumption and CVD events
(HR for 2 diet drinks/day group: 1.3; 95 % CI 1.11.5).
A significant unadjusted and adjusted interaction was ob-
served between baseline BMI and diet drink consumption for
the primary outcome (p=0.003 for both) (Online appendix).
On adjusted analysis, consumption of 2 diet drinks/day
continued to be significantly associated with occurrence of
CVD events in women with BMI 30 (HR 1.3, 95 % CI 1.1
1.6) and BMI < 25 (HR 1.7, 95 % CI 1.32.4), while the
association was not statistically significant in women with
BMI 2530 (HR 1.2, 95 % CI 0.91.5).
Finally, exclusion of HF from the primary outcome did not
change the hazard ratios significantly compared to the primary
analysis, and these continued to be statistically significant for
the 2 diet drinks/day group (Online appendix).
DISCUSSION
This study demonstrates an association between regular daily
intake of two or more diet drinks and CVD outcomes and
mortality in post-menopausal women. In our analysis, women
who consumed 2 diet drinks/day had a 30 % higher adjusted
risk of CVD events as well as overall mortality compared to
those with an intake of 03 diet drinks/month.
Our study, with nearly 60,000 subjects, is one of the largest
studies evaluating diet drink consumption and outcomes. Our
findings are concordant with the results of the only previous
report that expressly evaluated the risk of CVD events with diet
drink intake.
25
Gardener et al. used the Northern Manhattan
Study (NOMAS) cohort, and included 2,564 subjects (64 %
female). They found daily diet drink consumption to be asso-
ciated with an increased adjusted risk of CVD events (incident
stroke, MI or vascular death). The overall event rate was about
23 % over a mean follow-up of 9.8 years, which is significantly
higher than the total event rate of 7.1 % over 8.7 years in our
study; some of this may be explained by the presence of both
men and women in the NOMAS subject population, as well as
more ethnic diversity compared to the WHI cohort.
The results are also supported by other observational data
that have shown a link between diet drink consumption and
metabolic syndrome. Three separate reports, involving pa-
tients from the Framingham Heart Study, the Atherosclero-
sis Risk in Communities study and the Multi-Ethnic Study
of Atherosclerosis demonstrated significantly increased
rates of incident metabolic syndrome among subjects who
were frequent consumers of diet drinks.
2,8,9
Another report
that analyzed data from the San Antonio Heart Study noted a
greater incidence of obesity and a significantly higher
Table 3. Hazard Ratios for Primary and Secondary Outcomes
Across Diet Drink Consumption Strata
Models Outcomes
Cardiovascular events Cardiac death Overall death
HR (95 % CI) HR (95 % CI) HR (95 % CI)
Model I* N: 59,614 N: 59,447 N: 59,447
03/month 1.0 1.0 1.0
14/week 0.9 (0.91.02) 0.8 (0.70.99) 0.9 (0.80.9)
57/week 1.0 (0.91.1) 0.8 (0.60.99) 0.8 (0.80.9)
2/day 1.2 (1.041.3) 0.9 (0.71.2) 1.0 (0.91.1)
Model II
N: 55,073 N: 55,073 N: 55,073
03/month 1.0 1.0 1.0
14/week 1.0 (0.961.1) 1.0 (0.81.2) 1.0 (0.91.1)
57/week 1.1 (1.01.3) 1.1 (0.91.4) 1.1 (1.01.2)
2/day 1.6 (1.41.9) 1.8 (1.32.4) 1.5 (1.31.7)
Model III
N: 53,037 N: 53,037 N: 53,037
03/month 1.0 1.0 1.0
14/week 1.0 (0.91.1) 0.9 (0.81.1) 1.0 (0.91.1)
57/week 1.0 (0.91.1) 1.0 (0.81.3) 1.1 (1.01.2)
2/day 1.3 (1.21.5) 1.4 (1.041.9) 1.4 (1.21.6)
Model IV
§
N: 33,619
N: 33,619
N: 33,619
03/month 1.0 1.0 1.0
14/week 1.0 (0.91.1) 0.9 (0.71.2) 1.0 (0.91.1)
57/week 1.1 (0.91.2) 0.9 (0.71.3) 1.1 (0.91.2)
2/day 1.3 (1.11.5) 1.5 (1.032.3) 1.3 (1.041.5)
HR hazard ratios, CI confidence intervals
*Model I was unadjusted
Model II was adjusted for age, race, education and income
Model III was adjusted for the variables in Model II plus smoking
status, BMI, and a history of diabetes, hypertension and hyperlipidemia
§
Model IV was adjusted for the variables in Model III plus alcohol
intake, log calibrated energy intake, physical activity, sugar-sweetened
beverage intake, salt intake, and hormone therapy. Adjusted cardiac
event models were stratified on hypertension, and high cholesterol and
adjusted mortality models were stratified on hypertension and the
history of diabetes because these variables did not meet the proportional
hazards assumption
The majority of loss of patients in model 4 was secondary to missing
data for salt intake and calibrated energy
Table 4. Adjusted Hazard Ratios for Primary Outcome Across Diet
Drink Consumption Strata for Primary Analysis, for Baseline
Healthy Women, with Salt Intake and Calibrated Energy Intake
Excluded, and with Healthy Eating Index-2005 Included
Diet drink consumption
03/
month
14/
week
57/
week
2/day
HR
(95 % CI)
HR
(95 % CI)
HR
(95 % CI)
HR
(95 % CI)
Primary analysis*
N: 33,619 1.0
1.0 (0.91.1)1.1 (0.91.2)1.3 (1.11.5)
Baseline healthy
women
N: 22,417
1.0
1.0 (0.91.2)1.0 (0.81.2)1.2 (0.91.7)
Salt and calibrated
energy intake
excluded
N: 47,858
1.0
1.0 (0.91.1)1.0 (0.91.1)1.3 (1.11.5)
Healthy eating
index-2005 included
§
N: 44,869
1.0
1.0 (0.91.1)1.0 (0.91.2)1.3 (1.11.5)
HR hazard ratio, CI confidence interval
*Model IV: Adjusted for age, race, education, income, smoking status,
BMI, diabetes, hypertension, hyperlipidemia, alcohol intake, log
calibrated energy intake, physical activity, sugar-sweetened beverage
intake, salt intake, and hormone therapy
Model IV; Included women without a history of diabetes, hypertension,
and high cholesterol
Adjusted for Model IV excluding salt intake and calibrated energy
intake
§
Adjusted for Model IV including Healthy Eating Index-2005 scores and
excluding salt intake and calibrated energy intake
Vyas et al.: Diet Drinks and Cardiovascular EventsJGIM
increase in BMI with increasing intake of artificially sweet-
ened beverages, with an apparent dose response relationship
between the amount of artificially sweetened beverages
consumed and weight gain.
7
As both metabolic syndrome
and obesity are important risk factors for CVD, this may
contribute in part to the higher incidence of CVD events in
this population.
Exact pathophysiologic mechanisms that would explain the
association of weight gain, development of metabolic syn-
drome, and increased CVD events with diet soda consumption
are still unclear. One hypothesis is that artificial sweeteners
may increase the desire for sugar-sweetened, energy-dense
beverages/foods. Experimental data from animal (rat) models
suggests that consumption of products containing artificial
sweeteners may disrupt the correlation between sweet taste
and the energy content of foods (thus interfering with funda-
mental homeostatic and physiological processes).
26
Another
study investigating the functional magnetic resonance imaging
response to sucrose (a nutritive sweetener) and saccharin (a
nonnutritive sweetener) in diet soda drinkers versus non-diet
soda drinkers found alterations in the reward processing of
sweet taste in individuals who regularly consume diet soda.
27
An alternative explanation for this association could be
confounding by dietary patterns or incomplete adjustment
for confounders. In a recent study, diet beverage consumers
defined as having a healthy diet had a lower risk of metabolic
syndrome.
28
Analysis from the Health Professionals Follow-
Up Study presented evidence of an association between con-
sumption of sugar-sweetened beverages and increased CHD
risk and intermediate biomarkers, but no associations were
found for artificially sweetened beverage intake.
29
However,
the study noted that artificially sweetened beverage consump-
tion was associated with healthy lifestyle traits and higher
overall diet quality, which may suggest a role of dietary pattern
in the determination of outcomes. In addition, individuals
attempting to restrict energy intake and control weight may
be more likely to consider artificially sweetened beverages, a
factor that may influence CVD risk factor associations.
30
The
sensitivity analysis evaluating women without diabetes, hy-
pertension and high cholesterol at baseline was done to ad-
dress some of these questions. While the confidence intervals
widened (with loss of statistical significance), the hazard ratios
did not change significantly. Additionally, inclusion of the
HEI-2005 score, which is a validated tool for quantifying
dietary quality, also did not result in a significant change in
the association between diet drink consumption and CVD
events. Finally, the interaction between BMI and diet drink
intake noted in our analysis is an interesting finding that bears
further investigation, especially given other recent data that
highlight the role of body weight in this setting.
31
Limitations of this study include its observational nature,
and the fact that it involved retrospective analysis of data not
collected expressly for the purpose of this paper. It also in-
volves a specific population, that of post-menopausal women,
and thus may not be generalizable to other populations. As the
differences in demographic characteristics between women
excluded for missing diet drink data and the included women
demonstrate, presence of selection bias cannot be ruled out.
Due to limited data collection regarding diet drink intake after
the baseline evaluation, the analysis does not take into account
changes in consumption pattern over the course of follow-up.
Finally, the association seen in this study does not translate
into causality, and may be due to confounding variables that
were not examined in multivariate analysis, or may not even
be clearly defined as being confounders in this relationship as
of yet.
In conclusion, this study suggests an association between
consumption of two or more diet drinks per day and adverse
CVD events, as well as increased mortality. However, further
evaluation with other clinical studies, animal models and even
molecular and pharmacologic analyses is needed to confirm or
disprove this link, and to assess a possible causal relationship
between diet drink intake and increased CVD risk.
Funding Sources: The Division of Cardiovascular Medicine at the
University of Iowa Hospitals & Clinics and the Womens Health Initia-
tive provided partial funding for this manuscript.
Conflict of Interest: The authors declare that they do not have a
conflict of interest.
Relationship with Industry: None.
Corresponding Author: Ankur Vyas, MD; Division of Cardiovascular
MedicineUniversity of Iowa Hospitals Clinics, 200 Hawkins Dr., Int. Med.
E316-1 GH, Iowa City, IA 52242, USA (e-mail: ankurvyas7@gmail.com).
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... The order of magnitude obtained for the associations in this study is in line with the one traditionally observed in nutritional epidemiology studies for commonly consumed dietary factors, 72 77 78 and with the findings of WHO in its recent report, 8 which was based on meta-analyses of prospective cohort studies investigating intake of beverages containing artificial sweeteners. [25][26][27][28][29][30][31][32] Furthermore, in terms of public health perspectives, the opportunity of preventing even a moderate proportion of CVD events through reduced artificial sweetener intake is of high interest given the extensive use of these substances in products on the global market. Associations were consistent across the many sensitivity analyses we performed; they were also consistent with previous epidemiological literature on proxies of sweetener intakes (eg, artificially sweetened beverages) and in line with mechanistic insights from experimental studies. ...
... comparison with other studies Observational prospective studies on the associations between artificial sweeteners, assessed from the whole diet (in mg/day), and CVD risk are lacking; therefore, no direct comparison was possible. However, several studies have been conducted [25][26][27][28][29][30][31][32][33][34] and meta-analysed 8 22 35 36 73 79 using artificially sweetened beverage consumption as a proxy (in mL or serving/ day) and CVD risk. In line with recent results from the NutriNet-Santé study, 28 multiple cohorts found associations between artificially sweetened beverages and CVD. ...
... 33 These studies mostly took place in the United States 35 and have not been as extensively explored in European populations. In line with our results, the recent WHO meta-analyses 8 reported positive associations between the intake of beverages containing artificial sweeteners and cardiovascular events overall (hazard ratio 1.32, 95% confidence interval 1.17 to 1.50, three prospective studies [26][27][28] ) and more specifically for the incidence of stroke (1.19, 1.09 to 1.29, five prospective studies 25 27 29 31 32 ), but not for coronary heart disease (1.16, 0.97 to 1.39, four prospective studies 27 29 33 80 ). ...
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Objectives To study the associations between artificial sweeteners from all dietary sources (beverages, but also table top sweeteners, dairy products, etc), overall and by molecule (aspartame, acesulfame potassium, and sucralose), and risk of cardiovascular diseases (overall, coronary heart disease, and cerebrovascular disease). Design Population based prospective cohort study (2009-21). Setting France, primary prevention research. Participants 103 388 participants of the web based NutriNet-Santé cohort (mean age 42.2±14.4, 79.8% female, 904 206 person years). Dietary intakes and consumption of artificial sweeteners were assessed by repeated 24 h dietary records, including brand names of industrial products. Main outcomes measures Associations between sweeteners (coded as a continuous variable, log10 transformed) and cardiovascular disease risk, assessed by multivariable adjusted Cox hazard models. Results Total artificial sweetener intake was associated with increased risk of cardiovascular diseases (1502 events, hazard ratio 1.09, 95% confidence interval 1.01 to 1.18, P=0.03); absolute incidence rate in higher consumers (above the sex specific median) and non-consumers was 346 and 314 per 100 000 person years, respectively. Artificial sweeteners were more particularly associated with cerebrovascular disease risk (777 events, 1.18, 1.06 to 1.31, P=0.002; incidence rates 195 and 150 per 100 000 person years in higher and non-consumers, respectively). Aspartame intake was associated with increased risk of cerebrovascular events (1.17, 1.03 to 1.33, P=0.02; incidence rates 186 and 151 per 100 000 person years in higher and non-consumers, respectively), and acesulfame potassium and sucralose were associated with increased coronary heart disease risk (730 events; acesulfame potassium: 1.40, 1.06 to 1.84, P=0.02; incidence rates 167 and 164; sucralose: 1.31, 1.00 to 1.71, P=0.05; incidence rates 271 and 161). Conclusions The findings from this large scale prospective cohort study suggest a potential direct association between higher artificial sweetener consumption (especially aspartame, acesulfame potassium, and sucralose) and increased cardiovascular disease risk. Artificial sweeteners are present in thousands of food and beverage brands worldwide, however they remain a controversial topic and are currently being re-evaluated by the European Food Safety Authority, the World Health Organization, and other health agencies. Trial registration ClinicalTrials.gov NCT03335644
... Furthermore, 8 additional articles were identified from the reference lists of retrieved articles. Finally, 17 cohort studies were included in this systematic review ( Fig. 1) [13,14,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. ...
... Two studies included older adults aged ≥ 65 years only [23,24]. Nine studies were conducted in US adults [13,14,20,21,25,26,29,32,33], 5 studies in European adults [19,22,27,30,31], and 3 studies in Asian adults [23,24,28]. Most studies assessed the added sugar intake or its sources using a food-frequency questionnaire (FFQ) or dietary questionnaire. ...
... The estimates obtained after adjusting for potential confounders, including nutrients, demographic, anthropometric, medical, and lifestyle variables, were considered to identify associations of added sugar intake and its sources with mortality in this review. In terms of exposure of interest, 5 articles reported the findings on the associations between added sugar intake and mortality [13,14,23,24,30], and 15 articles reported the associations between food sources of added sugar and mortality [14,[19][20][21][22][25][26][27][28][29][30][31][32][33]. ...
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... Four prospective cohort studies (comprising five cohorts) reporting on the risk of cardiovascular disease mortality were included in meta-analyses (102,104,108,109). As assessed in prospective cohort studies, higher intakes of NSS-containing beverages were associated with a 19% increase in risk of cardiovascular disease mortality (Fig. 16). ...
... Three prospective cohort studies reporting on the risk of cardiovascular events were included in meta-analyses (108)(109)(110). As assessed in prospective cohort studies, higher intakes of NSScontaining beverages were associated with a 32% increase in risk of cardiovascular events 1 (Fig. 17). ...
... Cardiovascular events in Gardener et al. (2012) (108) included stroke, myocardial infarction and vascular death. In Vyas et al. (2015)(109), they included coronary heart disease, myocardial infarction, heart failure, coronary revascularization procedure, ischaemic stroke, peripheral artery disease and cardiovascular disease mortality. ...
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... All included studies were of good quality, with NOS scores of 7-9, except one of fair quality, with an NOS score of 6 (Table S10) [44]. Two studies that investigated the association between ASB and CVD used the same data sources as the present study but with different selection criteria [26,47]. Therefore, we narratively compared our findings with the results of these studies in the Discussion section. ...
... Moreover, at least one serving of ASB intake per day was significantly associated with total CVD (1.14 [1.03, 1.26]). The present study and the two previous publications from the WHI examined the association between ASB intake and CVD risk in a similar group of participants [26,47], although in the present study, we excluded participants with pre-existing CVD, diabetes, and cancer at baseline to minimize the issue of reverse causation. Interestingly, another recent meta-analysis of cohort studies used change analyses of repeated measures of intake and substitution analyses to investigate the association of low-and no-calorie sweetened beverages (LNCSBs) consumption with cardiometabolic outcomes, revealing that substitution of LNCSBs for SSBs was associated with lower body weight, lower obesity and CHD incidence, and lower risk of CVD mortality [51]. ...
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... Meta-analysis results of artificial sweeteners intake for all-cause mortality (HR: hazard ratio; RR: relative risk; CI: Confidence Interval)[37][38][39]41,[43][44][45][46]. ...
... Meta-analysis results of artificial sweeteners intake for all-cause mortality (HR: ratio; RR: relative risk; CI: Confidence Interval)[37][38][39]41,[43][44][45][46]. ...
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Cancer has become a major challenge in the global disease burden. Artificial sweeteners are a class of chemical compounds that are used as food and beverage addition agent to replace sugar. However, the health effects of consuming artificial sweeteners are still unclear. This meta-analysis was performed to evaluate the role of artificial sweeteners on cancer. The databases PubMed, Cochrane Library, MEDLINE, Web of Science and EMBASE were searched up until July 2022. A Newcastle–Ottawa scale (NOS) was used to estimate the study quality. A total of 25 observational studies were included with a total of 3,739,775 subjects. The intake of artificial sweeteners had no apparent association with overall cancer incidence and mortality. However, in Europe, artificial sweeteners’ intake could increase the risk of cancer incidence (HR/RR = 1.07, 95% CI = [1.02, 1.12], I2 = 25.8%, P = 0.223), which appears to be related to a shift in nutritional behaviors in the countries. Significant results were also observed in subgroups with aspartame and a mixed intake of artificial sweeteners. Moreover, higher risk was observed for artificial sweeteners intake in all-cause mortality (HR/RR =1.13, 95% CI = [1.03, 1.25], I2 = 79.7%, p < 0.001) and a J-shaped association between them was found. More data from well-conducted studies and clinical trials are required.
... All 7 studies (Mullee et al. 2019;Malik et al. 2019;Mossavar-Rahmani et al. 2019;Vyas et al. 2015;Paganini-Hill, Kawas, and Corrada 2007;Anderson et al. 2020;Zhang et al. 2021) were included in the meta-analysis of highest category versus lowest category. The pooled HR was 1.12 for all-cause mortality (95% CI: 1.05 to 1.20; I 2 ¼78%), 1.13 for CVD mortality (95% CI: 1.03 to 1.24; I 2 ¼0%), and 1.02 for cancer mortality (95% CI: 0.92 to 1.13; I 2 ¼50%). ...
... Our search initially yielded 15,002 records and finally included 13 eligible articles, including 14 cohorts in the meta-analysis (Mullee et al. 2019; Odegaard et al. 2015; Malik et al. 2019; Mossavar-Rahmani et al. 2019; Ramne et al. 2019; Collin et al. 2019;Barrington and White 2016;Vyas et al. 2015;Khan et al. 2004;Tasevska et al. 2014;Paganini-Hill, Kawas, and Corrada 2007;Anderson et al. 2020;Zhang et al. 2021) ( 1Figure 1). Supplementary ...
... So far, much scientific attention has been aroused to the positive correlation between SSB intake and weight gain [3], diabetes [8] and coronary heart disease [9,10]. Previous longitudinal studies have focused on the female population [11], elderly population [12], the population with gastrointestinal tumors [13] or populations in certain occupations [14], and several studies have been conducted in the last century [15,16]. Two previous studies from the National Health and Nutrition Examination Survey (NHANES) declared that higher SSB intake was associated with higher all-cause mortality and mortality of cardiovascular disease (CVD) [15,17]. ...
... Daily consumption of artificially sweetened beverages, pure fruit juices, unsweetened tea and coffee, plain water, non-or lowfat milk, and sweetened milk were also computed for substitution analysis. One serving of beverage was defined as 12 oz standard [11,14,32,33]. Moreover, the US Department of Agriculture (USDA) Dietary Research Nutrition Database and Food Patterns Equivalence Database were used to determine added sugars from SSBs, total daily energy intake, vegetables, fruits, grains, red meat and processed meat [14,17]. ...
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Background: The relationship between intake of sugar-sweetened beverages (SSBs) and the risk of death in patients with chronic kidney disease (CKD) is unclear. We evaluated the association between SSB intake and subsequent overall mortality in CKD patients. Methods: We included data from 3996 CKD patients who participated in the 1999-2014 National Health and Nutrition Examination Survey (NHANES). SSB intake was assessed by a 24-h dietary recall, grouped as none, >0 to <1 serving/day, 1 to <2 servings/day and ≥2 servings/day. After adjusting for demographic variables, lifestyle, diet and comorbidities, Cox proportional risk regressions were applied to analyze the associations between the daily intake of SSBs as well as added sugar from beverages and all-cause mortality. Results: In the whole research population, the median age at baseline was 67 years, 22% were Black and 54% were female. A total of 42% had stage 3 CKD. During an average follow-up period of 8.3 years, a sum of 1137 (28%) deaths from all causes was recorded. The confounder-adjusted risk of mortality was associated with an increase of 1 serving/day of SSBs, with all-cause mortality of 1.18 [95% confidence interval (95% CI)1.08-1.28], and intakes of increased 20-g added sugar/1000 kcal of total energy per day were associated with all-cause mortality of 1.14 (1.05-1.24). Equivalently substituting 1 serving/day of SSBs with unsweetened coffee [HR (95% CI) 0.82 (0.74-0.91)], unsweetened tea [HR (95% CI) 0.86 (0.76-0.98)], plain water [HR (95% CI) 0.79 (0.71-0.88)], or non- or low-fat milk [HR (95% CI) 0.75 (0.60-0.93)] were related to a 14-25% reduced risk of all-cause mortality. Conclusion: Findings suggest that in the CKD population, increased SSB intake was associated with a higher risk of mortality and indicated a stratified association with dose. Plain water and unsweetened coffee/tea might be possible alternatives for SSBs to avert untimely deaths.
... Artificial sweeteners were developed by the food industry in the context of a dramatic increase in the incidence of obesity to reduce calorie and, specifically, added sugars intake [57,58]. However, evidence on the negative health effects of artificial sweeteners' intake is accumulating, such as the association with cardiovascular disease and mortality [59], and with increased cancer risk [60]. Unfortunately, many in the general public still adopt the use of sweeteners as a short-term strategy to reduce dietary sugar and for weight management [61]. ...
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Cooking is crucial to the achievement of healthy eating habits, and the internet, as host of culinary recipes websites, is a medium for the dissemination of cooking-related content. Research has revealed that most recipes available on internet sites do not have healthy characteristics when compared to recommendations for healthy eating, even the ones promoted as ‘healthy’. This study investigated culinary recipes available on the ‘healthy eating’ section of a popular Brazilian recipe-sharing website. Recipes (n = 814) were analyzed with a validated framework based on national dietary guidelines. Ingredients (n = 5887) were classified according to the extension and purpose of their industrial processing. The recipes’ titles were content analyzed to identify the health-related words and phrases used. Recipes contained ultra-processed foods and not enough unprocessed or minimally processed foods, such as legumes (4.7%, n = 380), nuts and seeds (18.4%, n = 150), and fruits (n = 32.7%, n = 263). The recipes’ titles mentioned 564 health-related terms, appealing to physical characteristics, including weight loss, and fads, such as gluten-free, dukan, low-carb, detox, fitness, ripped body, and belly burner. Therefore, the ‘healthy’ recipes available on the Brazilian recipe-sharing website presented many aspects not in accordance with national dietary guidelines.
... The sex-specific difference might be explained by physiologic differences between men and women, e.g., sex hormones and lipid profile, but further research is warranted [28][29][30]. However, not all studies are in line with our findings, which might be due to differences in study methodology, such as in SSB definition (i.e., including juice, added sugar) and age of included participants [27,[31][32][33][34][35]. ...
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Purpose Examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice (FJ) consumption and all-cause mortality in Dutch adults. Methods Data of 118,707 adults participating (mean age = 45 years; 60% was women) the Lifelines Cohort Study were prospectively analyzed. Dietary intake was assessed using a validated food-frequency questionnaire. Participants’ vital status was followed-up until February 2022 via the National Personal Records Database. Associations between beverages of interest and all-cause mortality risk were investigated using restricted cubic spline and Cox proportional hazard regression analyses, including substitution analyses. Models were adjusted for demographics, lifestyle, and other dietary factors. Results During follow-up (median = 9.8 years), a total of 2852 (2.4%) deaths were documented. Median (IQR) of SSB, LNCB, and FJ consumption were 0.1 (0.0–0.6), 0.1 (0.0–0.6), and 0.2 (0.0–0.6) serving/day, respectively. Dose–response analyses showed linear associations between SSB, LNCB, and FJ consumption and mortality risk. For each additional serving of SSB and LNCB, HRs of all-cause mortality risk were 1.09 (95% CI 1.03–1.16) and 1.06 (95% CI 1.00–1.11). Replacing SSB with LNCB showed a nonsignificant association with a lower mortality risk, particularly in women (HR 0.91, 95% CI 0.81–1.01). Finally, an inverse association between FJ and all-cause mortality was observed at moderate consumption with HR of 0.87 (95% CI 0.79–0.95) for > 0–2 servings/week and HR of 0.89 (95% CI 0.81–0.98) for > 2–< 7 servings/week when compared to no consumption. Conclusions Our study showed adverse associations between SSB consumption and all-cause mortality. Replacing SSB with LNCB might be associated with lower mortality risk, particularly in women. Moderate intake of FJ was associated with lower all-cause mortality risk.
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Sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and 100% fruit juices are frequently consumed and have been documented that they could lead to serious disease burden. However, inconsistent evidence on the association between SSBs, ASBs, and 100% fruit juices consumption and mortality have been presented. PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and PsycINFO were systematically searched. We conducted a random-effects meta-analysis and dose-response meta-analysis to assess the association and calculated the pooled hazard ratio with 95% confidence interval. And we evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Thirteen studies with 1,539,127 participants proved eligible. An SSB-consumption increase per 250 mL/day was associated with a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 8% greater risk of cardiovascular disease mortality (3 more per 1000 persons; low certainty). ASB-consumption increase per 250 mL/day demonstrated a 4% greater risk of all-cause mortality (5 more per 1000 persons; low certainty) and 4% greater risk of cardiovascular disease mortality (2 more per 1000 persons; low certainty). The association of SSBs and ASBs with cancer mortality was not significant, with a very low certainty of evidence. There was evidence of a linear dose-response association between SSB intake and cancer mortality, as well as between ASB intake and all-cause mortality and cancer mortality. We observed a non-linear dose-response association between ASB intake and CVD mortality and SSB intake and all-cause and CVD mortality. Low certainty of evidence demonstrated that per 250 mL/day consumption increase in SSBs and ASBs had a small impact on all-cause and cardiovascular disease mortality but not on cancer mortality. The association of 100% fruit juice consumption with all-cause and cardiovascular disease mortality was uncertain.
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Background: Few studies have evaluated whether adherence to dietary recommendations is associated with mortality among cancer survivors. In breast cancer survivors, we examined how postdiagnosis Healthy Eating Index (HEI)-2005 scores were associated with all-cause and cause-specific mortality. Methods: Our prospective cohort study included 2,317 postmenopausal women, ages 50 to 79 years, in the Women's Health Initiative's Dietary Modification Trial (n = 1,205) and Observational Study (n = 1,112), who were diagnosed with invasive breast cancer and completed a food frequency questionnaire after being diagnosed. We followed women from this assessment forward. We used Cox proportional hazards models to estimate multivariate-adjusted HRs and 95% confidence intervals (CI) for death from any cause, breast cancer, and causes other than breast cancer, according to HEI-2005 quintiles. Results: Over 9.6 years, 415 deaths occurred. After adjustment for key covariates, women consuming better quality diets had a 26% lower risk of death from any cause (HRQ4:Q1, 0.74; 95% CI, 0.55-0.99; Ptrend = 0.043) and a 42% lower risk of death from non-breast cancer causes (HRQ4:Q1, 0.58; 95% CI, 0.38-0.87; Ptrend = 0.011). HEI-2005 score was not associated with breast cancer death (HRQ4:Q1, 0.91; 95% CI, 0.60-1.40; Ptrend = 0.627). In analyses stratified by tumor estrogen receptor (ER) status, better diet quality was associated with a reduced risk of all-cause mortality among women with ER(+) tumors (n = 1,758; HRQ4:Q1, 0.55; 95% CI, 0.38-0.79; Ptrend = 0.0009). Conclusion: Better postdiagnosis diet quality was associated with reduced risk of death, particularly from non-breast cancer causes. Impact: Breast cancer survivors may experience improved survival by adhering to U.S. dietary guidelines.
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... 8. Ludwig DS, Peterson KE, Gortmaker SL. Relation between consumption of sugar - sweetened drinks and childhood obesity : a prospective, observational analysis. Lancet. 2001;357:505-508.pmid:11229668. ...
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Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover 3 main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors, to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all 3 study designs and 4 are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available at www.annals.org and on the Web sites of PLoS Medicine and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.
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Background: Temporal increases in the consumption of sugar-sweetened beverages have paralleled the rise in obesity prevalence, but whether the intake of such beverages interacts with the genetic predisposition to adiposity is unknown. Methods: We analyzed the interaction between genetic predisposition and the intake of sugar-sweetened beverages in relation to body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) and obesity risk in 6934 women from the Nurses' Health Study (NHS) and in 4423 men from the Health Professionals Follow-up Study (HPFS) and also in a replication cohort of 21,740 women from the Women's Genome Health Study (WGHS). The genetic-predisposition score was calculated on the basis of 32 BMI-associated loci. The intake of sugar-sweetened beverages was examined prospectively in relation to BMI. Results: In the NHS and HPFS cohorts, the genetic association with BMI was stronger among participants with higher intake of sugar-sweetened beverages than among those with lower intake. In the combined cohorts, the increases in BMI per increment of 10 risk alleles were 1.00 for an intake of less than one serving per month, 1.12 for one to four servings per month, 1.38 for two to six servings per week, and 1.78 for one or more servings per day (P<0.001 for interaction). For the same categories of intake, the relative risks of incident obesity per increment of 10 risk alleles were 1.19 (95% confidence interval [CI], 0.90 to 1.59), 1.67 (95% CI, 1.28 to 2.16), 1.58 (95% CI, 1.01 to 2.47), and 5.06 (95% CI, 1.66 to 15.5) (P=0.02 for interaction). In the WGHS cohort, the increases in BMI per increment of 10 risk alleles were 1.39, 1.64, 1.90, and 2.53 across the four categories of intake (P=0.001 for interaction); the relative risks for incident obesity were 1.40 (95% CI, 1.19 to 1.64), 1.50 (95% CI, 1.16 to 1.93), 1.54 (95% CI, 1.21 to 1.94), and 3.16 (95% CI, 2.03 to 4.92), respectively (P=0.007 for interaction). Conclusions: The genetic association with adiposity appeared to be more pronounced with greater intake of sugar-sweetened beverages. (Funded by the National Institutes of Health and others.).
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Objectives: We examined national patterns in adult diet-beverage consumption and caloric intake by body-weight status. Methods: We analyzed 24-hour dietary recall with National Health and Nutrition Examination Survey 1999-2010 data (adults aged ≥ 20 years; n = 23 965). Results: Overall, 11% of healthy-weight, 19% of overweight, and 22% of obese adults drink diet beverages. Total caloric intake was higher among adults consuming sugar-sweetened beverages (SSBs) compared with diet beverages (2351 kcal/day vs 2203 kcal/day; P = .005). However, the difference was only significant for healthy-weight adults (2302 kcal/day vs 2095 kcal/day; P < .001). Among overweight and obese adults, calories from solid-food consumption were higher among adults consuming diet beverages compared with SSBs (overweight: 1965 kcal/day vs 1874 kcal/day; P = .03; obese: 2058 kcal/day vs 1897 kcal/day; P < .001). The net increase in daily solid-food consumption associated with diet-beverage consumption was 88 kilocalories for overweight and 194 kilocalories for obese adults. Conclusions: Overweight and obese adults drink more diet beverages than healthy-weight adults and consume significantly more solid-food calories and a comparable total calories than overweight and obese adults who drink SSBs. Heavier US adults who drink diet beverages will need to reduce solid-food calorie consumption to lose weight.
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Ein Großteil der biomedizinischen Forschung ist beobachtend, und die Qualität der veröffentlichten Berichte über diese Forschung ist oft unzureichend. Dies behindert die Beurteilung der Stärken und Schwächen einer Studie und ihrer Übertragbarkeit. Die Strengthening the Reporting of Observational Studies in Epidemiology (STROBE-) Initiative hat Empfehlungen entwickelt, was in einem akkuraten und vollständigen Bericht einer Beobachtungsstudie enthalten sein sollte. Die Empfehlungen wurden von uns so definiert, dass sie 3 Hauptstudientypen abdecken: Kohorten-, Fallkontroll- und Querschnittsstudien. Im September 2004 veranstalteten wir einen zweitägigen Workshop mit Methodikern, Forschern und Herausgebern wissenschaftlicher Zeitschriften, um eine Checkliste zu entwerfen. Anschließend wurde der Entwurf bei mehreren Treffen der Koordinierungsgruppe und nach E-Mail-Diskussionen mit der erweiterten STROBE-Gruppe revidiert und dabei empirische Evidenz und methodologische Aspekte berücksichtigt. Das Ergebnis des Workshops und des anschließenden iterativen Prozesses aus Beratung und Revision war eine Checkliste von 22 Punkten (STROBE-Statement), die sich auf die Bereiche Titel, Abstract, Einleitung, Methoden, Ergebnisse und Diskussion eines Artikels beziehen. 18 der Punkte sind relevant für alle 3 Studiendesigns, während 4 der Punkte spezifisch für Kohorten-, Fallkontroll- und Querschnittsstudien sind. Ein ausführlicher Begleitartikel (Explanation and Elaboration) wurde separat veröffentlicht und ist auf den Webseiten von PLoS Medicine, Annals of Internal Medicine und Epidemiology frei zugänglich. Wir hoffen, dass das STROBE-Statement dazu beitragen kann, dass Beobachtungsstudien besser berichtet werden.