Soft drink consumption and obesity: it is all about fructose

George A. Bray
Pennington Center, Louisiana State University, Baton
Rouge, Louisiana, USA
Correspondence to George A. Bray, MD, 6400 Perkins
Road, Baton Rouge, LA 70808, USA
Tel: +1 225 763 3176; e-mail: brayga@pbrc.edu
Current Opinion in Lipidology 2010, 21:51–57
Purpose of review
The purpose of the review is to suggest that fructose, a component of both sucrose
(common sugar) and high fructose corn syrup, should be of concern to both healthcare
providers and the public.
Recent findings
Consumption of sugar-sweetened beverages has increased steadily over the past
century and with this increase has come more and more reports associating their use
with the risk of overweight, diabetes and cardiometabolic disease. In a meta-analysis of
the relationship between soft drink consumption and cardiometabolic risk, there was a
24% overall increased risk comparing the top and bottom quantiles of consumption.
Several factors might account for this increased risk, including increased carbohydrate
load and increased amounts of dietary fructose. Fructose acutely increases
thermogenesis, triglycerides and lipogenesis as well as blood pressure, but has a
smaller effect on leptin and insulin release than comparable amounts of glucose. In
controlled feeding studies, changes in body weight, fat storage and triglycerides are
observed as well as an increase in inflammatory markers.
Summary
The present review concludes on the basis of the data assembled here that in the
amounts currently consumed, fructose is hazardous to the cardiometabolic health of
many children, adolescents and adults.

Keywords
beverages, health risk, high fructose corn syrup, obesity, sucrose, weight gain

Curr Opin Lipidol 21:51–57

ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
0957-9672

after oral administration [7
,8
], it is reasonable to lump

Introduction
Sucrose intake has risen steadily for more than 200 years
[1]. With this increase in sucrose has come an increased
intake of fructose, as fructose is half the sucrose molecule.
Prior to the domestication of the sugar plant, some 1500
years ago, fructose in the human diet came primarily from
fruits and vegetables [2]. Following the development of
soft drinks a century ago, sugar intake has increased even
more as it was the principal sweetener used in these
beverages until after World War II. Consumption of
sugar-sweetened beverages (SSBs) is still rising around
the world and in the USA, it has increased from 11.8% of
calories in 1965 to over 20% of calories by 2002 [3]. The
most recent estimates of soft drink consumption for US
children and adults put the figures at 154 and 142 kcal per
day, respectively [4,5]. Fructose is half of the consumed
sucrose or high fructose corn syrup (HFCS) and is esti-
mated to be an average of 54.7 g per day (range 38.4–72.8)
and accounts for a mean of 10.2% of total caloric intake.
Adolescents, in whom consumption is highest (12–18
years), consume an average of 72.8 g per day (12.1% of
total calories) of fructose [6
]. One-quarter of adolescents
consume more than 15% of their calories from fructose
[6
]. As HFCS and sucrose have similar metabolic profiles
0957-9672 ß 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins
them together as the major sources of dietary fructose –
the central focus of this review.
As the use of caloric sweeteners has continued to rise,
more and more reports suggest that they may cause
weight gain in some adults [9–14,15
,16

,17–24,25
].
Reports also suggest that the increasing intake of soft
drinks is associated with an increase in the risk of diabetes
[10,14,15
,26–28,29
] and the risk of cardiometabolic
disease [14,29
–31
] and gout [32
]. The intake of fruc-
tose is related to lipid disturbances in small dense LDL
cholesterol in children [33].
Studies comparing glucose and fructose have suggested
that fructose is much more likely to be the culprit for
these diseases than glucose. The studies supporting
effects of fructose and caloric sweeteners in the obesity
epidemic and reports of cardiovascular and metabolic risk
will be summarized in five categories:
(1) Response to acute exposure to fructose or sucrose.
(2) Response to fructose or sucrose in short-term studies
lasting up to 12 weeks.
(3) Meta-analyses of soft drink consumption.
DOI:10.1097/MOL.0b013e3283346ca2

Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
 52 Nutrition and metabolism
(4) Experimental studies of fructose and fat.
(5) Potential mechanisms for responses to fructose.
In preparing this review, Medline was searched for papers
relating to fructose and beverages and obesity. Two
meta-analyses [34,35] were also examined for additional
relationships and this topic has been discussed previously
by the author [5,35,36].
Dietary fructose comes from two principal sources [6
],
foods such as fruits and vegetables, and from refined
products that contain sucrose or HFCS. The growth of
fructose in our diet during the past century has come
through adding sucrose (sugar) or HFCS to foods. To
help distinguish these two sources of fructose, I have
labeled those in naturally occurring fruits and vegetables
as ‘good fructose’ and the fructose that comes from
sucrose or HFCS as ‘bad fructose’.
Acute studies
Several studies have examined the effects of single doses
of fructose versus glucose on energy expenditure [37,38],
serum lipids [39–42,43
,44

,45
,46

], leptin [42,47],
insulin [42,47] and blood pressure [48]. From these
studies, it is clear that fructose increases thermogenesis,
triglycerides and blood pressure. In one study, a 75 g oral
load of glucose or fructose was given to 17 volunteers and
metabolic changes followed for 4 h. Fructose stimulated
oxygen consumption more than glucose but produced
a much smaller stimulation of insulin [37]. Fructose
increased the respiratory quotient more than glucose, a
finding that may imply increased de-novo lipogenesis.
Blockade of the sympathetic nervous system with pro-
panolol, a b-adrenergic blocking drug, reduced oxidation
of both fructose and glucose by about 40%. Of interest,
both obese and diabetic patients had a similar stimulation
of oxygen uptake after infusion of glucose that was
smaller than the response to fructose [49]. In the most
recent study to evaluate the acute effects of fructose on
lipids [46

], 17 healthy obese men (N ¼ 9) and women
(N ¼ 8) with a BMI more than 30 kg/m2 were admitted to
the Clinical and Translational Research Center for a
cross-over study lasting 24 h, in which mixed meals
and beverages with 30% fructose or 30% glucose were
given and blood samples drawn periodically. The area
under the curve of insulin, leptin and triglyceride was
measured. The rise in plasma glucose was smaller after
fructose, but the rise in triglycerides and lactate was
larger. Insulin and leptin both showed a lower response
to fructose than to glucose. These responses in lipids are
seen primarily in men with small or no response in
women [50,51]. The lipogenic effects of fructose pro-
bably lie in its pathways of hepatic metabolism. Fructose
is phosphorylated at the 1 position (F-1-P), in contrast
to glucose, which is phosphorylated at the 6 position
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
(G-6-P). This F-1-P is a ready substrate for enolase which
cleaves it to triose phosphates that serve as the backbone
of triglycerides. In contrast, glucose 6-P must be con-
verted to glucose-1,6-diphosphate before it is a substrate
for enolase.
The acute response of blood pressure to fructose was
examined in 15 healthy men who drank, on three
occasions, 500 ml volumes of water (placebo) or 60 g of
fructose or glucose. Blood pressure, metabolic rate and
autonomic nervous system activity were measured for
2 h. Administration of fructose was associated with an
increase in both systolic and diastolic blood pressure.
Blood pressure did not rise after either glucose or water
[48]. This rise in blood pressure acutely is consistent with
the rise in blood pressure noted in the 10-week study
described below [52].
Intermediate length studies
Several intermediate length feeding studies have
examined the effects of glucose and fructose [43
,44

,
50,52,53]. In one of these, 41 overweight men and women
entered a 10-week parallel arm study. Twenty-one
received 3.4 MJ (813 kcal) of sugar-containing beverages
and were compared with 20 others who received bev-
erages sweetened with aspartame, containing about 1 MJ
(240 kcal) and no sugar [52]. For their other foods, the
participants could select freely from items available at a
kiosk run by the study group. After 10 weeks, energy
intake had increased by 1.6 MJ per day (581 kcal per day)
and sucrose to 28% of calorie intake in the group receiv-
ing the sugar-containing beverages. Protein and fat
intakes declined [52]. Body weight and fat mass increased
by 1.6 and 1.3 kg, respectively in the sugared-beverage
group and decreased by 1.0 and 0.3 kg in the aspartame-
sweetened group. Blood pressure increased by 3.8/
4.1 mmHg in the sugared-beverage-consuming group
but it did not change in the aspartame group. Concen-
trations of several inflammatory markers were also chan-
ged [54]. In the group consuming sucrose, haptoglobin
increased by 13%, transferrin by 5% and C-reactive
protein by 6%. In the group receiving the aspartame-
sweetened beverages, haptoglobin decreased by 16%,
C-reactive protein decreased by 26% and transferrin
was basically unchanged with a small 2% fall [54]. An
increase in inflammatory markers also occurs when the
quantity of rapidly absorbed carbohydrates, that is, those
with a high glycemic load, is increased, and this com-
ponent of soft drinks may be another reason for its
association with cardiometabolic disease [55–59].
In a study of similar length, fructose and glucose were
compared by replacing 25% of the calories with either a
glucose-containing drink or a fructose-containing drink
for 10 weeks, 8 weeks as outpatients and 2 weeks as

inpatients at the end of the study. Thirty-two men and
women ate a 15% protein, 30% fat and 55% carbohydrate
diet. Fifteen received 25% of calories as the glucose-
sweetened beverages and 17 received 25% of kcal as
the fructose-sweetened beverage. Visceral fat increased
by 14% in the fructose-consuming group compared
with about 5% in the control group with no significant
change in body weight or subcutaneous fat. De-novo
lipogenesis increased and postprandial triglycerides
increased, particularly at night [7
].
Meta-analyses of beverage consumption
Several meta-analyses relating soft drink consumption
to changes in energy intake, changes in body weight or
risk of cardiometabolic diseases have been published
[34,60

]. In the study by Vartanian et al. [34], the
magnitude of the relationship between the beverage
intake and body weight was expressed as the effect size
or ‘r value’. An effect size of 0.1 was small, an effect size
of 0.25 was moderate and an effect size of 0.4 as large
(Table 1). In the studies examining the relationship
between soft drink consumption and body weight,
Vartanian et al. [34] found that outcomes from the cross-
sectional studies varied depending on how body weight
was expressed. When the focus was on the association
between soft drink consumption and BMI, two studies
reported a significant positive association, whereas nine
did not. Two studies revealed a positive association
between soft drink consumption and body fat percentage,
but one study did not. In addition, four studies showed that
people’s risk of being overweight or obese was positively
associated with their soft drink consumption (Table 1).
Other studies reported a positive association between soft
drink consumption and body weight and ponderal index
but not skinfold thickness. In 11 cross-sectional studies,
they found a significant positive relationship in two, but
not in nine others, and there were no studies in which
drinking beverage was associated with a significant
reduction in BMI. Among longitudinal studies that have
examined the association between soft drink consumption
and change in body weight or BMI, one was positive, two
were mixed and four showed no association. Of seven
experimental studies, five reported a positive association
with weight. Effect sizes, which represent the magnitude
of the relationship between the beverage intake and body
Table 1 Average effect size of soft drink consumption by type of research design
Cross-sectional studies Longitudinal studies
Research design r (95% CI) No. r (95% CI)
Energy intake 0.13 (0.12–0.14) 12 0.24 (0.23–0.26)
Body weight 0.06 (0.03–0.08) 12 0.03 (0.00–0.06)
Adapted from Tables 1, 2 and 3 with permission [34]; r, average effect size calculated using version 2 of the comprehensive meta-analysis software
program. The authors of this paper considered an effect size of 0.1 as a small effect, an effect size of 0.25 as medium and an effect size of 0.4 as large.
CI, confidence interval; No., number of studies in meta-analysis.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Soft drink consumption and obesity Bray 53
weight, were moderate (0.24; Table 1). The effect sizes for
change in body weight were, in general, smaller than the
effects on energy intake as soft drinks are only one source
of calories. In cross-sectional studies, the effect size was
only 0.06, in longitudinal studies it was 0.03 and in short
experimental studies, it was 0.24.
A second meta-analysis of soft drink intake and weight
gain reported by Olsen and Heitmann [60

] included
some additional studies. A total of 14 prospective and five
experimental studies were identified. The majority of the
prospective studies found positive associations between
intake of calorically sweetened beverages and obesity.
Three experimental studies found positive effects of
calorically sweetened beverages and subsequent changes
in body fat, but two experimental studies did not. Eight
prospective studies adjusted for energy intake. Seven of
these studies reported associations that were essentially
similar before and after energy adjustment. The authors
concluded that a high intake of calorically sweetened
beverages is a determinant for obesity.
There are a number of other studies suggesting that soft
drinks may be related to cardiometabolic diseases. There
are six studies that have shown relationships between soft
drink consumption and the risk of developing diabetes
[11,15
,26–28,29
]. Most of the studies use a contrast
between lowest and highest intake. Three studies show a
relationship of soft drink consumption to the risk of
developing the metabolic syndrome [14,29
,30
]. One
study shows that soft drink consumption is related to
risk of developing coronary heart disease and one that
fructose intake is related to the risk of developing gout in
men [32
].
Experimental studies of fructose and fat
In two animal experiments, there is a clear interaction
between fructose intake and the response to a high fat
diet. In one experiment [61], groups of C57Bl mice were
fed one of four diets: a trans-fat diet with mouse chow at
30% of calories and fat at 45% of calories (28% saturated,
57% monounsaturated, 13% polyunsaturated fatty acids
(PUFAs) and 3% trans fats with access water); the trans-
fat diet with access to 55/45 HFCS solution in water/gel at
42 g/l placed in petri dishes in the bottom of the cage; a
Short experimental studies Overall effect size
No. r (95% CI) No. r (95% CI) No.
5 0.24 (0.16–0.31) 9 0.16 (0.15–0.16) 22
6 0.24 (0.18–0.28) 7 0.06 (0.05–0.08) 25
 54 Nutrition and metabolism
30% chow diet with Lard replacing the fat mixture above;
and a standard mouse chow diet with ad lib access to
water. Over the 16 weeks, mice fed the trans-fat diet with
HFCS to drink gained the most, with the Lard þ HFCS
not significantly less. When HFCS was omitted from the
trans-fat diet, the weight gain was greater than chow
alone, but significantly less than with the combination
of the HFCS and trans-fat diet. Fatty accumulation and
inflammatory changes were observed most in the trans-fat
and HFCS diet group.
In another experiment [62], rats were begun on a 64%
starch or 65% fructose diet for 6 months and then tested
for their response of food intake in intraperitoneal leptin.
The weight gain was identical in these two groups, but
the animals eating the high fructose diet had markedly
impaired response to leptin and an increase in one of the
suppressors of cytokine signaling (SOCS-3) in the hypo-
thalamus, which reduces the response to leptin. For the
final 2 weeks, half the rats in each group were provided a
diet with 60% Lard and 7% sucrose and the others
continued on their previous diets. The rats exposed to
fructose for 6 months had a significantly greater gain in
body fat on the high fat diet (14.1 g) than those previously
eating the starch diet (9.1 g).
Potential mechanisms for the detrimental
effects of fructose
Several mechanisms have been suggested for the effects
of fructose that come from drinking either HFCS or
sucrose-sweetened beverages. The inadequate reduction
in caloric intake of solid foods when calorie-sweetened
beverages are ingested is one of these mechanisms [63–
66,52,67,68,69,70,71,72
]. In acute feeding studies, SSBs
failed to reduce energy intake, in contrast to water [73].
A second mechanism is that fructose is metabolized prim-
arily in the liver where it is converted to fructose-1-phos-
phate from which it can readily become a substrate for the
backbone of the triglyceride molecule [74]. Third, the
metabolism of fructose in the liver generates adenosine
5’phosphate that is a substrate for conversion to uric acid
through a process that alters nitric oxide generation. The
enhanced production of uric acid by the liver may con-
tribute to the relation of uric acid to cardiovascular disease
[75

]. Another mechanism is the increase in blood pres-
sure that is observed with acute administration of fructose
that is not seen with glucose [48] and the increase in blood
pressure over 10 weeks when individuals drank SSBs as
contrasted with aspartame-sweetened beverages [52]. A
final potential mechanism is the differences in gene
expression following fructose administration [53].
Soft drinks are clearly a part of our culture and their
consumption has risen steadily for more than 50 years. A
20-ounce soft drink made with HFCS has about 250 kcal.
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Thus, an extra 20-ounce soft drink each day is probably
enough to account for the increased body weight over the
last quarter of a century [76
]. Soft drinks are a prominent
part of the fast food culture. When individuals eat at a fast
food restaurant, compared to a day when they do not, the
fast food day has a larger intake of soft drinks and French
fries and a smaller intake of cereal, vegetables and milk
[77].
Soft drink consumption and milk consumption are inver-
sely related [34,36]. As soft drink consumption has
increased, the consumption of milk, a major source of
calcium, has decreased. In the meta-analysis of cross-
sectional studies by Vartanian et al. [34], the effect size
was small, but in the longitudinal studies, it was moder-
ate. Milk, particularly low-fat milk, is a valuable source of
calcium for bone growth during the time of maximal bone
accretion, and, as part of the Dietary Approach to Stop
Hypertension (DASH) diet, may be helpful in lowering
blood pressure [78]. Reducing consumption of beverages
containing HFCS or glucose–fructose (sucrose) might
reverse this pattern of decreased milk consumption.
The rising consumption of calorie-sweetened beverages
provides a rising intake of fructose with all of its potential
negative biological effects. Based on this review of the
literature, this reviewer concludes that in the amounts
currently consumed, fructose is hazardous to the cardio-
metabolic health of many children, adolescents and
adults. An increase in the risk of diabetes mellitus,
metabolic syndrome, coronary heart disease and gout
has been reported with higher consumption of soft drinks.
This increase is opposite in direction to the highly
significant reduction of about one-quarter in the first
event rate for nonfatal myocardial infarction or coronary
death in patients treated with simvastatin in the Heart
Protection Study [79]. Replacing fructose-containing
beverages with healthier alternatives [80] such as water
would be an important strategy in the battle of the bulge
and its cardiometabolic consequences [81

].
Conclusion
In summary, it seems clear that fructose, a component of
both sucrose (common sugar) and HFCS, in the amounts
now consumed should be of concern to both healthcare
providers and the public. The growing evidence of its
association with the risk of overweight, diabetes and
cardiometabolic disease is highlighted in meta-analyses
of the relationship between soft drink consumption and
cardiometabolic risk. Several factors might account for
this increased risk, including increased carbohydrate
load and the increased amounts of fructose that are
components of both sucrose (table sugar) and HFCS.
Fructose acutely increases thermogenesis, triglycerides
and lipogenesis as well as blood pressure, but has a

smaller effect on leptin and insulin release than compar-
able amounts of glucose. In controlled feeding studies,
changes in body weight, fat storage and triglycerides are
observed as well as an increase in inflammatory markers.
This reviewer concludes on the basis of the data
assembled here that in the amounts currently consumed,
fructose is hazardous to the cardiometabolic health of
many children, adolescents and adults. Although we need
more evidence about whether there is a ‘threshold’ effect
for fructose, we also need more work on how to help
consumers switch to healthy beverages and sweeteners.
References and recommended reading
Papers of particular interest, published within the annual period of review, have
been highlighted as:

of special interest


of outstanding interest
Additional references related to this topic can also be found in the Current
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 56 Nutrition and metabolism
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