Editorial
Sugar-Sweetened Beverage and Vascular Function
Not So Sweet After All
Prediman K. Shah
S ugar-sweetened beverages (SSBs) are some of the most
commonly consumed beverages around the world.
Sweeteners used in these beverages include sucrose, fruit
juices, and high fructose corn syrup. Increased consumption
of these beverages has been causally linked to obesity, dia-
betes mellitus/metabolic syndrome, hypertension, gout, and
cardiovascular disease.15 On the basis of a comparative risk
analysis model, Micha et al4 concluded that, in 2012 in the
United States, 45% of 702308 deaths attributed to heart dis-
ease, stroke, and type 2 diabetes mellitus were associated with
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consumption of 10 dietary factors, with consumption of SSB
accounting for 7.4% of cardiometabolic deaths. The consump-
tion of SSB accounted for 10.8% of deaths from coronary
heart disease and 14.8% of type 2 diabetes mellitusrelated
deaths.4
See accompanying article on page 1250
These adverse effects of SSB consumption may be medi-
ated through increased glycemic load, obesity, insulin resis-
tance, type 2 diabetes mellitus, increased oxidative stress,
inflammation, and vascular dysfunction.15 Endothelial dys-
function is considered to be one of the potential mediators of
adverse cardiovascular effects of SSB.6 Normal healthy vascu-
lar endothelium mediates vasodilation, exhibits an antithrom-
botic/profibrinolytic phenotype, and inhibits inflammation
by its antiadhesive properties against circulating leucocytes,
thereby maintaining vascular health. Endothelial dysfunction
is often a precursor of and is associated with atherosclerotic
cardiovascular disease. Although previous studies have shown
that endothelial dysfunction can be induced by acute hyper-
glycemia,7 detailed examination of the acute effects of con-
suming an SSB on microvascular and large vessel function has
not been systematically performed.4
In this issue of Arteriosclerosis, Thrombosis, and Vascular
Biology, Loader et al8 report the acute effects of consuming
an SSB on micro- and macrovascular vasomotor function in
12 healthy volunteers in comparison with a placebo using a
randomized single-blind crossover design. The authors used
laser speckle contrast imaging to measure cutaneous micro-
vascular blood flow at baseline and during a vasodilator
From the Oppenheimer Atherosclerosis Research Center, Cedars-Sinai
Heart Institute, Los Angeles, CA; and Department of Medicine, Cedars Sinai
Medical Center, University of California at Los Angeles School of Medicine.
Correspondence to Prediman K. Shah, MD, Division of Cardiology,
Cedars-Sinai Medical Center, 8700 Beverly Blvd, Room 5531, Los
Angeles, CA 90048. E-mail shahp@cshs.org
(Arterioscler Thromb Vasc Biol. 2017;37:1020-1021.
DOI: 10.1161/ATVBAHA.117.309450.)
2017 American Heart Association, Inc.
Arterioscler Thromb Vasc Biol is available at http://atvb.ahajournals.org
DOI: 10.1161/ATVBAHA.117.309450
1020
stimulus provided by iontophoretically delivered acetylcho-
line (an endothelium-dependent vasodilator) and sodium
nitroprusside (an endothelium-independent direct smooth
muscle relaxant and vasodilator). Macrovascular function
was assessed using ultrasonographic monitoring of brachial
artery diameter changes in response to both transient arte-
rial occlusion followed by release (reactive hyperemia, an
endothelium-dependent vasodilator stress) and nitroglycerin
(an endothelium-independent direct vasodilator stimulus).
Furthermore, the authors conducted additional in vivo and
ex vivo experiments in rats given intraperitoneal sucrose to
simulate an SSB load, and they examined vascular vasodilator
function at baseline and in response to endothelium-dependent
and endothelium-independent vasodilators. The authors also
examined the role of oxidative stress in the adverse effects of
sugar load on vascular function by measuring reactive oxy-
gen species and evaluating the effects after pretreatment with
the antioxidants N-acetylcysteine and the NADPH inhibitor
apocyanin.8
Overall, the results of these investigations and experiments
showed that acute hyperglycemic load, triggered by consumption
of SSB, rapidly leads to impaired endothelium-dependent micro-
vascular and macrovascular vasodilation compared with placebo
in human subjects, with similar results observed in rats given
intraperitoneal sucrose loads.8 In contrast, direct smooth muscle
relaxation (endothelium-independent vasodilator effect) was not
significantly affected by SSB consumption. Furthermore, in rats,
pretreatment with antioxidants prevented the adverse effects of
SSB on endothelium-dependent vasodilator response in vivo and
in vitro, implicating acute oxidative stress in the vascular dys-
function caused by the acute sugar load. The authors went on
to show that in rats, the nitric oxide bioavailability was reduced
by the sucrose-induced acute oxidative stress, contributing to
reduced endothelium-dependent vasodilator response. However,
no change in vascular eNOS or phosphorylated eNOS levels was
noted in response to sucrose loading in rats.
Overall, the authors provide fairly compelling evidence to
support their conclusions that acute glycemic load induced by
SSB consumption in man impairs acute endothelium-depen-
dent vasodilator responses in the microvasculature, as well as
in large arteries. The experiments with rats indicate that this
effect is likely to be related to acute oxidative stress impairing
nitric oxide bioavailability.
However, some limitations of the study should be pointed
out. First, only male volunteers were included, making it
difficult to know whether similar effects would have been
observed in females as well. Vascular function may vary based
on racial/ethnic origin, and therefore, results cannot necessar-
ily be extrapolated to all racial/ethnic groups. The authors
used a short-term randomized trial design, and it is unclear
 Shah Sweet Beverage and Vascular Function 1021
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Figure. Potential mechanisms by which sugar-sweetened beverage (SSB) consumption increases cardiometabolic risk. CVD indicates
cardiovascular disease.
whether longer-term cumulative exposure would cause a more
permanent vascular dysfunction that outlasts the actual dura-
tion of hyperglycemic exposure. The authors only studied the
vasomotor component of vascular function, and it remains
unclear whether other aspects of endothelial function, such as
thrombogenicity or leukocyte-endothelial adhesiveness, could
have been altered as well. How hyperglycemic load creates
oxidative stress was not explored in this study. Furthermore, it
is conceivable that habitual consumption of SSB may produce
additional adverse vascular effects such as structural vascular
remodeling that would not necessarily be observed in short-
term single exposure experiments as reported by Loader et al.8
Notwithstanding these limitations, the authors provide
a significant contribution to the field of vascular biology by
investigating the potential mechanisms by which SSB con-
sumption could directly affect vascular function at the level
of both large arteries and the microcirculation. The increased
cardiovascular risk associated with SSB consumption is likely
multifactorial (increased weight gain, dyslipidemia, increased
risk of insulin resistance and type 2 diabetes mellitus, hyper-
tension, gout, inflammation) but also could be attributed, in
part, to direct vascular effects, such as endothelial dysfunc-
tion, as described by Loader et al8 (Figure).
Increased awareness of the cardiometabolic health hazards
of SSB consumption is warranted, particularly considering the
high consumption of SSB around the world and the poten-
tial for risk mitigation with reduced consumption of SSB.
The good news is that in the United States, between 2002 and
2012, population-adjusted cardiometabolic deaths dropped
by 26.5%, which was in part associated with and potentially
attributable to reduced consumption of SSB.5 Public health
efforts to discourage consumption of SSB and potentially
replace them with more healthy beverages, such as coffee and
tea (without added sugar or cream), as suggested by Malik and
Hu,5 may be warranted. SSBs may not be so sweet after all.
Disclosures
None.
References
1. Huang C, Huang J, Tian Y, Yang X, Gu D. Sugar sweetened beverages
consumption and risk of coronary heart disease: a meta-analysis of
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biomarkers of risk in men. Circulation. 2012;125:17351741.
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Association between dietary factors and mortality from heart disease,
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924. doi: 10.1001/jama.2017.0947.
5. Malik VS, Hu FB. Fructose and cardiometabolic health: what the evi-
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6. Loader J, Montero D, Lorenzen C, Watts R, Mziat C, Reboul C, Stewart
S, Walther G. Acute hyperglycemia impairs vascular function in healthy
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7. Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson
DC, Creager MA. Acute hyperglycemia attenuates endothelium-depen-
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8. Loader J, Meziat C, Watts R, Lorenzen C, Siguado-Roussel D, Stewart S,
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KEY WORDS: Editorials endothelium endothelium, vascular oxidative
stress rats sucrose
 Sugar-Sweetened Beverage and Vascular Function: Not So Sweet After All
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Prediman K. Shah

Arterioscler Thromb Vasc Biol. 2017;37:1020-1021

doi: 10.1161/ATVBAHA.117.309450
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