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 ﬁnding of an association between low-calorie
soda intake and stroke risk should be interpreted with caution,
because we previously did not ﬁnd 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
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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