-
1
The
effect
of
fructose
consumption
on
plasma
cholesterol
in
adults:
a
meta-
analysis of controlled feeding
trials
1,2,3
Tao
An
4,5
, Rong Cheng
Zhang
4,5
, Yu Hui
Zhang
4
, Qiong
Zhou
4
, Yan
Huang
4
, Jian
Zhang
4,
*.
4
State Key
Laboratory of Cardiovascular Disease, Fuwai
Hospital, National Center
for
Cardiovascular Diseases, Chinese Academy of
Medical Sciences and Peking
Union
Medical College, Beijing, China
5
Tao An and Rong
Cheng Zhang contributed equally to this study.
Supplemental
Table
1
and
supplemental
Figures
1-4
are
available
as
Online
3
Supporting Material with the online
posting of this paper at
RUNNING TITLE: Fructose and cholesterol
WORD COUNT: 5618; NUMBER OF FIGUREA: 3;
NUMBER OF TABLES: 2
SUPPLEMENTARY
MATERIAL: Online Supporting Materials: 5
AUTHOR LIST FOR INDEXING: An, Zhang,
Zhang, Zhou, Huang, Zhang
1
The study was supported by
the Ministry of Science and Technology of China
with
grant of the National High-tech
Research and Development Program of China to Dr
Jian Zhang.
1
2
2
Author disclosures: T. An,
R.C. Zhang, Y
.H. Zhang, Q. Zhou,
Y
. Hung, J. Zhang
have no
conflicts of interest.
* To whom
correspondence should be addressed. Mailing
address: Heart Failure
Center,
Cardiovascular Institute and Fuwai Hospital,
Chinese Academy of Medical
Sciences and
Peking Union Medical College, 167 Beilishilu,
Beijing, China; Zip code:
100000;
Telephone number: 86-10-88396180; Fax number:
86-10-88396180; E-mail:
Fwzhangjian62@
PROSPERO REGISTRATION
NUMBERS: CRD42012003351
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ABSTRACT
Fructose is widely
used as a sweetener in production of many foods,
yet the relation
between fructose
intake and cholesterol remains uncertain. We
performed a systematic
review
and
meta-analysis
of
human
controlled
feeding
trials
of
isocaloric
fructose
exchange
for
other
carbohydrates
to
quantify
the
effects
of
fructose
on
total
cholesterol (TC), LDL cholesterol
(LDL-C), and HDL cholesterol (HDL-C) in adult
humans.
Weighted
mean
differences
were
calculated
for
changes
from
baseline
cholesterol
concentrations by using
generic inverse
variance random-effects models.
The
Heyland
Methodological
Quality
was
used
to
assess
study
quality.
Subgroup
analyses and meta-regression were
conducted to explore possible influence of study
characteristics. Twenty-four trials
(with a total of 474 subjects) were included in
our
meta-analysis. In an overall pooled
estimate, fructose exerted no effect on TC, LDL-C
and
HDL-C.
Meta-
regression
analysis
indicated
that
fructose
dose
was
positively
correlated
with
the
effect
sizes
of
TC
and
LDL-C.
Subgroup
analyses
showed
that
isocaloric
fructose
exchange
for
carbohydrates
could
significantly
increase
TC
by
12.97 mg/dL
(95%CI: 4.66, 21.29;
P
=
0.002) and LDL-C by 11.59 mg/dL (95%CI:
4.39, 18.78;
P
=
0.002) at >100g fructose/d but had no effect on TC
and LDL-C when
fructose
intake
was
≤
100g/d.
In
conclusion,
very
high
fructose
intake
(>100g/d)
could
lead
to
significantly
increase
in
serum
LDL-C
and
TC.
Larger,
longer
and
higher-quality human controlled feeding
trials are needed to confirm these results.
Key words:
fructose,
cholesterol, meta-analysis
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INTRODUCTION
Hyperlipidemia is
a common
risk factor for coronary heart disease (CHD), with
44.4%
of
adults
in
the
United
States
having
abnormal
TC
values
and
32%
having
elevated LDL-C levels
(1). Compared to subjects with normal blood lipid,
those with
hyperlipidemia have a 3-fold
risk of heart attacks (2). Lifestyle modification
should be
initiated
in
conjunction
both
primary
and
secondary
prevention
of
CHD.
More
consideration exists as to what
constitutes healthy eating.
Fructose is
the most naturally occurring monosaccharide, and
has become a major
constituent
of
our
modern
diet.
Fruit,
vegetables,
and
other
natural
sources
provide
nearly one-third of dietary fructose,
and two-thirds come from beverages and foods in
the
diets
(eg,
candies,
jam,
syrups,
etc)
(3).
Fructose
is
preferred
by
many
people,
especially those
with diabetes mellitus because of its low glycemic
index (23% versus
glucose 100%) (4).
After intestinal uptake, fructose is mainly
removed from the blood
stream
by
the
liver
in
an
insulin-
independent
manner,
and
is
used
for
intrahepatic
production of
glucose, fatty acids or lactate. Cross-sectional
studies in human suggest
that
excessive
fructose
consumption
can
lead
to
adverse
metabolic
effects,
such
as
dyslipidemia
and
increased
visceral
adiposity
(5-7).
The
Dietary
Guidelines
for
Americans, 2010, point out that it is
lack of sufficient evidence to set a tolerable
upper
intake
of
carbohydrates
for
adults
(8).
Although
The
Candian
Diabetes
Association
suggests
consumption of no more than 60g of added fructose
per day by people with
diabetes for its
triglyceride-raising effect (9), the threshold
dose of fructose at which
the adverse
influence on cholesterol is controversial.
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To determine the effect
of fructose on cholesterol, a substantial number
of clinical
trials
have
been
performed
on
adult
humans
with
different
health
status
(diabetic,
obese,
overweight,
hyperinsulinemic,
impaired
glucose-tolerant
and
healthy).
These
trials used various intake levels of
fructose and different protocols. Thus, it is
difficult
to
reach
a
consistent
conclusion
across
these
studies.
Therefore,
we
conducted
a
systematic review of the scientific
literature and meta-analysis of controlled feeding
trials to evaluate the effect of
isocaloric oral fructose exchange for
carbohydrates on
cholesterol and to
clarify the active factors of fructose.
Materials and Methods
This
meta-analysis
followed
the
Preferred
Reporting
Items
for
Systematic
Reviews
and Meta-analyses
(PRISMA) criteria (10).
Search
strategy.
We
searched
PubMed
(/pubmed;
from
1966 to December 2012),
Embase (; from 1966 to December
2012)
and
the
Cochrane
Library
database
()
by
using
the
following search terms:
fructose and (lipemia or lipaemia or lipids or
cholesterol or
“
total
cholesterol
”
or
“
LDL
cholesterol” or
“
HDL
cholesterol”
)
in
English. We also
searched
China
National
Knowledge
Infrastructure
()
and
Wangfang
database () in Chinese according to the
search strategy. The
search was
restricted to reports of trials on humans.
Study
selection.
All
clinical
trials
using
fructose
and
indexed
within
the
above
databases
were
collected.
Two
independent
reviewers
(T.A.,
R.C.Z)
screened
the
abstracts
and
titles
for
initial
inclusion.
If
this
was
not
sufficient,
full
texts
articles
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were obtained and reviewed by at least
two independent reviewers (T.A., R.C.Z, Q.Z.,
Y
.H.). The reference lists
of retrieved articles also used to supplement the
database.
Any disagreements were
resolved through discussion. We included
controlled feeding
trials
investigating
the
chronic
effect
of
fructose
on
blood
cholesterol,
from
both
randomized
and
nonrandomized
studies,
if
they
met
the
following
criteria:
subjects
must
have
been
administered
fructose
for
at
least
2
weeks;
studies
investigated
the
effect of oral free (unbound,
monosaccharide) fructose when compared with
isocaloric
control diet with another
carbohydrate in place of fructose; studies were
performed in
human adults with either a
parallel or crossover design; subjects in both
experimental
groups
and
control
groups
were
instructed
to
consume
isocaloric
diets.
If
the
study
reported any comparisons, we included
all such comparisons in the meta-analysis.
Data extraction and quality
assessment.
Two reviewers
(T.A., R.C.Z) independently
extracted
relevant data from eligible studies. Disagreements
were resolved by one of
the
two
authors
(Y
.H.Z.,
J.Z.).
These
data
included
information
on
study
features
(author,
year
of
publication,
study
design,
randomization,
blinding,
sample
size,
comparator,
fructose
form,
dose,
follow-up
and
macronutrient
profile
of
the
background
diet),
participant
characteristics
(gender,
age
and
healthy
status)
and
baseline
and
final
concentrations
or
net
changes
of
total
cholesterol,
LDL-C
and
HDL-C. Data initially
extracted were converted to system international
unit (eg, TC: 1
mmol/L
converted
to
38.6
mg/dL).
For
multi-arm
studies,
only
intervention
groups
that
met
inclusion
criteria
were
used
in
this
analysis.
If
blood
lipid
concentrations
were
measured
several
times
at
different
stages
of
trials,
only
final
records
of
lipid
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concentrations at the end of the trials
were extracted for this meta-analysis.
The quality of each study was assessed
with the Heyland Methodological Quality
Score (MQS) (11), generalized as
follows: randomization; analysis; blinding;
patient
selection; comparability of
groups at baseline; extent of follow up; treatment
protocol;
co-intervention;
outcomes.
The
highest
score
for
each
area
was
two
points.
Higher
numbers represented a
better quality
(MQS≥8).
Data synthesis.
Statistical analyses were performed
with Stata software (version 11.0;
StataCorporation,
TX,
USA)
and
REVMAN
software
(version
5.2;
Cochrane
Collaboration,
Oxford,
United
Kingdom).
Separate
pooled
analyses
were
conducted
by using the
generic inverse variance random-effects models
even where there was no
evidence
of
between-study
heterogeneity
because
these
models
give
more
conservative
summary
effect
estimates
in
the
presence
of
undetected
residual
heterogeneity than fixed-effects
models. The different changes from baseline
between
fructose
and
carbohydrate
comparators
for
total
cholesterol,
LDL
cholesterol
and
HDL
cholesterol
were
used
to
estimate
the
principle
effect.
We
applied
paired
analyses to all crossover trials
according to the methods of Elbourne and
colleagues
(12).
Weighted
mean
differences
of
fructose
consumption
on
cholesterol
concentrations
and corresponding 95% CIs were calculated. A
2-sided
P
value <0.05
was
set
as
the
level
of
significance
for
an
effect.
The
variances
for
net
changes
in
serum
cholesterol were only reported directly in two
trials (29, 31). We calculate net
changes
for
other
studies
by
using
the
means
±
SDs
cholesterol
concentrations
at
baseline
and
at
the
end
of
intervention
period
(13).
SDs
were
calculated
from
SEs
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when
they
were
not
directly
given.
If
these
data
were
unavailable,
we
extrapolated
missing SDs by
borrowing SDs derived from other trials in this
meta-analysis (14). In
addition,
we
assumed
a
conservative
degree
of
correlation
of
0.5
to
impute
the
change-from-baseline
SDs,
with
sensitivity
analyses
performed
across
a
range
of
possible
correlation
coefficients
(0.25
and
0.75)
(13).
For
crossover
trials
in
which
only final measurements were included,
the differences in mean final measurements
were
assumed
on
average
to
be
the
same
as
the
differences
in
mean
change
scores
(13). Inter-study
heterogeneity was tested by the
Cochrane
’s
Q-test
(
P
< 0.1), and was
quantified by the
I
2
statistic, where
I
2
≥
50% was evidence of substantial heterogeneity.
To explore the potential effects of
factors on the primary outcomes and investigate
the
possible
sources
of
heterogeneity,
we
performed
meta-regressions
and
predefined
subgroup
analyses
stratified
by
comparator,
dose,
study
duration,
randomization,
health status, study design and study
quality. As for studies used a range of fructose
doses, the average doses calculated on
the basis of the average reported energy intake
or
weight
of
participants
(28.5
calories
per
kilogram
of
body
weight).
Sensitivity
analyses
were
also
performed
according
to
the
Cochrane
Handbook
for
Systemic
Review
.
Funnel
plots
and
Egger’s
linear
regression
test
were
conducted
to
detect
publication bias.
RESULTS
Based
on
our
search
criteria,
1602
eligible
studies
were
identified,
and
1565
studies
were excluded on review of the titles and
abstracts. The remaining 37 studies
were retrieved and fully reviewed.
Fifteen of these did not meet the inclusion
criteria
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and were
excluded in the final analysis. A total of 22
studies (providing data for 24
trials)
involving
474
subjects
(15-36)
were
included
in
the
meta-analysis
(
Supplemental Fig. 1, Table
1
).
The
reports
of
Koh
and
Reiser
(22,
23)
included
two
trials
(bringing
the
total
number
of trials to 24). Eleven trials were randomized
(17, 18, 20, 21, 25, 27-29, 31,
34,
36). Nineteen trials used crossover (15-19,
21-32), and five used parallel designs
(20, 33-36). As for the 19 cross-over
trials, 10 trials have reported the washout period
(16, 18, 22, 25, 27-31), 9 trials did
not have washout period (15, 17, 19, 21, 23, 24,
26,
32). The trials varied in size,
from 8 to131 subjects. The mean age of trial
participants
ranged from 26.7 to 64.4
years. Seventeen trials (15, 17-23, 25, 27, 28,
30, 31, 34, 36)
were performed in
outpatient settings, 3 trials (26, 29, 32) in
inpatient settings, and 4
trials
in
both
outpatient
and
inpatient
settings
(16,
24,
33,
35).
Nine
trials
were
conducted on diabetic
subjects (19-21, 24-27, 29, 30), 8 trials in
healthy subjects (17,
18, 22, 23, 28,
31, 34, 35), 3 trials in overweight/obese subjects
(32, 33, 36), 2 trials in
hyperinsulinemic
subjects
(16,
23),
1
trial
in
those
who
were
impaired
glucose-tolerant (22), and 1 trial in
subjects with type IV hyperlipoproteinaemia (HLP)
(15). Background diets were 42-55%
carbohydrate, 25-38% fat, and 13-20% protein.
The carbohydrate comparators choose
starch in 13 trials (15, 16, 21, 23-25, 27-30, 32,
36),
glucose
in
6
trials
(22,
31,
33-35),
sucrose
in
3
trials
(17,
18,
26),
and
mixed
carbohydrates in two trials (19, 20).
Four trials used fructose in crystalline (16, 18,
20,
21), 5 trials in
liquid
(19, 32-35),
and
15 trials
in
mixed form
(15, 17,
22-31). The
reported
mean
baseline
serum
TC
ranged
from
170
to
230.8
mg/dl,
LDL-C
ranged
9
10
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
from 90.7 to 157 mg/dl,
and HDL-C ranged from 35.1 to 57.1 mg/dl. Nineteen
trials
reported
the
fructose
intake
among
background
diet
was
not
different
between
the
fructose and control
groups, in which 15 trials reported the background
fructose intake
account for
≤
3% of total
energy (9 to 24g) (15-23, 29, 32, 33,
35)
, while 4 trials did
not
report the proportion of it (24, 25, 26, 34). Four
trials used background fructose
≤
3%
(3.2
to
18g)
of
total
energy
in
the
control
groups,
but
put
total
fructose
into
consideration in the
fructose group (27, 28, 30-31).
Only
o
ne trial reported less than
20g
(4.3
%
of
total
energy)
fructose
was
consumed
among
basal
diet
(36).
The
baseline
values
were
not
provided
in
5
trials
(19,
22,
23).
The
median
fructose
dose
in
the
available trials
included in our meta-analysis was 79.25 g/d
(range: 30-182 g/d), and
the duration
varied from 2 to 26 weeks.
The quality
scores of each study ranged from 6 to 9. Fifteen
trials were classified
as
high
quality
(MQS≥8),
and
8
trials
were
of
low
quality
(17,
19,
26,
30,
32-35).
Only
three trials were blinded, one single-blinded (34)
and 2 double-blinded (29, 35).
Eight
trials
(19,
21,
24,
26-30)
received
industry
funding.
Three
studies
with
four
trials (15, 16, 22) did not report any
information about financial conflicts of interest.
Effect of fructose on
cholesterol
Total
cholesterol.
Twenty-two
trials
(16-34,
36)
reported
the
value
of
TC,
and
the
pooled
estimate was 2.47 mg/dL (95% CI: -3.04, 7.98;
P
= 0.38) without
statistically
heterogeneity
(heterogeneity Chi
2
= 28.14,
I
2
=
25%,
P
= 0.14)
(
Fig. 1
). The residual
sources
of
heterogeneity
were
investigated
by
meta-regression
models.
Univariate
meta-regression
showed that the fructose dose was positively
related to TC, even after
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11
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190
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192
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194
195
196
197
198
199
adjusted for study
duration and health status
(regression coefficient = 0.18; 95% CI:
0.06,
0.31,
P
=
0.008)
(
Table
2
)
.
The
dose-response
relation
between
fructose
consumption
and
TC
largely
explained
the
residual
heterogeneity
of
the
effect.
Subsequently,
we
stratified
fructose
dose
≤
60,
>60
to
100,
and
>100
as
moderate,
high,
and
very
high,
respectively,
according
to
Candian
Diabetes
Association
and
reference ranges for
fructose (9, 37, 38). Fructose could significantly
increase TC by
12.97
mg/dL
(95%CI:
4.66,
21.29;
P
=
0.002)
when
fructose
intakes
were
>100g/d
but
had no effect on TC if fructose was given lower
than 100g. Predefined subgroup
analyses
were conducted by study characteristics
(
Supplemental Table 1
).
Sensitivity
analyses
according
to
possible
correlation
coefficients
(0.25
and
0.75)
and
systematically removal of each
individual trial
did not alter the
overall analysis and
analyses
stratified by dose.
LDL
cholesterol.
The mean change
for LDL cholesterol in nineteen trials (15, 16,
18,
20, 22, 23, 25-35) was 3.76 mg/dL
(95% CI: -1.07, 8.6;
P
=
0.13) without statistically
heterogeneity (heterogeneity
Chi
2
= 19.85,
I
2
=
9%,
P
= 0.34)
(
Fig. 2
). The residual
sources
of
heterogeneity
were
investigated
by
meta-regression
models.
Univariate
meta-regression
showed that the fructose dose was positively
related to LDL-C, even
after adjusted
for comparators, study duration and health
status
(regression
coefficient
= 0.15; 95% CI: 0.03, 0.28,
P = 0.02)
(
Table
2
). The dose-response relation between
fructose consumption and LDL-C largely
explained the residual heterogeneity of the
effect. We stratified fructose dose
according to CDA and reference ranges for fructose
(9,
37,
38).
Fructose
intake
>100g/d
could
significantly
increase
LDL-C
by
11.59
11
12
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
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216
217
218
219
220
221
mg/dL
(95%CI:
4.39,
18.78;
P
=
0.002).
Predefined
subgroup
analyses
were
conducted by other study
characteristics (
Supplemental Table
1
). Sensitivity analyses
across
possible
correlation
coefficients
(0.25
and
0.75)
did
not
alter
the
overall
analysis and analyses stratified by
dose. The removal of Cybulska et al resulted in a
significant LDL-C-raising effect in the
overall analysis (
P
= 0.03).
HDL
cholesterol.
The
result
of
HDL
cholesterol
was
calculated
based
on
24
trials
(15-36), the mean
difference was -0.56 mg/dL (95% CI: -2.05, 0.93;
P
= 0.46) without
heterogeneity
(heterogeneity
Chi
2
=
21.85,
I
2
=
0%,
P
=
0.53)
(
Fig.
3
).
Meta-
regression
analysis
did
not
show
significant
effect
modifier
of
HDL-C.
Predefined subgroup
analyses were conducted by study characteristics
(
Supplemental
Table
1
). Sensitivity analyses according to
possible correlation coefficients (0.25 and
0.75)
and
systematically
removal
of
each
individual
trial
did
not
alter
the
overall
analysis.
Publication bias
Funnel
plots
and
Egger’s
test
indicated
no
significant
publication
bi
as
in
the
meta-analyses
of
TC,
LDL
cholesterol,
and
HDL
cholesterol
(TC
Egger’s
test:
P
=
0.881;
LDL
cholesterol
Egger’s
test:
P
=
0.815;
HDL
cholesterol
Egger’s
test:
P
=
0.484)
(
Supplemental Figs. 2-4
).
DISCUSSION
This
meta-
analysis
of
24
controlled
feeding
trials
with
477
subjects
found
no
effect
on
TC,
LDL-C
and
HDL-C
when
fructose
was
substituted
for
other
carbohydrates.
Residual
heterogeneity
was
detected
by
meta-regression
for
this
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243
outcome that fructose dose was
positively correlated with the effect sizes of TC
and
LDL-C.
The present meta-
analysis is consistent with a prospective 2-year
trial on chronic
effect
of
fructose
from
Turku
sugar
studies
XI,
which
did
not
report
any
change
in
cholesterol
for
those
individuals
who
consumed
more
than
100g
fructose/d
(39).
Aeberli et al reported another
prospective, randomized, 3-week controlled
crossover
trial
in
which
healthy
young
men
were
fed
80
g/d
free
fructose,
and
found
a
significant atherogenic LDL subclass
distribution (40). However, there was an average
of
34g
combined
fructose
consumed
among
basal
foods
in
this
study,
which
meant
subjects consumed fructose over 110g/d.
The median dose of fructose available in our
meta-analysis was
≈
79.25 g/d, it was higher
than 90th percentile (78 g/d) and lower
than 95th percentile (87 g/d) in the
United States, reported by the National and Health
and
Nutrition
Examination
Survey
III
(41).
As
for
subjects
with
diabetic
mellitus,
Sievenpiper et al did not report
cholesterol-raising effect if the fructose dose
was >60
g/d
(median:
97.5
g/d)
in
their
meta-analysis
(42).
The
result
of
our
study
and
intervention trials may
be supported the idea that fructose did not
increase cholesterol
for the subjects
with generalizable levels of exposure.
The results of subgroup analyses showed
that the effects of fructose intake on TC
and
LDL-C
were
significant
as
the
fructose
dose
>
100g/d.
An
intake
of
100g/d
is
approximately equal to
400kcal/d or 20% of energy intake for a sedentary
person with
an energy requirement of
2000 kcal/d. The doses for cholesterol-raising
effect account
for less than 10 percent
of intake in males and females aged 19 to 22
years, the group
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14
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245
246
247
248
249
250
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252
253
254
255
256
257
258
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260
261
262
263
264
265
with the highest level of exposure in
the United States (41). Another study found that
the
upper
quintile
of
Americans
consume
more
than
110g
fructose
daily
as
added
sugar
or
as
high-fructose
corn
syrup
(43).
Although
a
small
number
of
people
consume
fructose
at
very
high
dose,
it
is
necessary
to
advise
them
to
change
their
lifestyle.
The
dose-dependent
effect
on
triglyceride
was
also
reported
in
a
recent
meta-analysis
that
concluded
the
same
dose
threshold
of
100g/d
for
a
triglyceride-increasing effect of
fructose on fasting triglyceride level in adult
humans
(38).
For
healthy
subjects
who
consumed
150g
of
fructose/day,
endogenous
cholesterol
synthesis
and
the
fat
content
of
viscera
and
liver
have
been
shown
to
increase
(44).
All
evidences
have
proved
that
fructose
is
proposed
to
have
adverse
effects at very high
or excessive doses. The mechanism of the
cholesterol increase by
fructose might
be due to increased levels of advanced glycation
end products, which
cause
damage
to
LDL
and
make
it
poorly
recognized
by
lipoprotein
receptors
and
scavenger
receptors
(45).
Furthermore,
excess
exposure
to
fructose
can
damage
the
function
of
adipocytes
and
may
reduce
the
recycling
of
cholesterol
extracted
from
serum
LDL.
Studies have shown that
elevated uric
acid might
contribute to
LDL-C
increases, and this
effect can be reduced by allopurinol (46).
Based on the composition of added
sugars in the United States where the fructose:
glucose
ratio
is
close
to
0.43,
and
the
NHANES
1999
–
2004
estimates
(41),
the
increase
of
fructose
consumption
is
always
accompanied
with
an
increase
in
total
energy intake. Persons
consuming >100g/d of sugars are potentially eating
in excess
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15
266
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287
of their
energy requirement (47), and then overweight and
obesity could result. So we
can
not
suggest
that
it
is
safe
to
only
limit
fructose
to
<100g/d
in
coronary
heart
disease
management
and
prevention.
It
may
need
to
take
into
account
the
other
components of foods that accompany the
fructose. This dose threshold effects on TG
and LDL-C can only help better inform
nutritional guidance and avoid inappropriate
marketing of carbohydrates.
Our
meta-analysis
did
not
show
significant
effect
of
fructose
on
HDL-C.
However,
Perez-Pozo
et
al
(46)
reported
a
significant
HDL-C-lowing
effect
in
74
adult
men
fed
with
200g
fructose/d
in
a
randomized,
2-week
crossover
trial,
suggesting that excessive fructose dose
intake can also
affect
HDL-C.
Further trials
are needed to find the threshold of
fructose on HDL-C.
There are several limitations to our
work. First, many trials had a relatively small
sample size, and most of them were
funded by industry
which can affect the
quality of
studies
. Second,
the change of fructose in the background diet can
affect the practical
utility of the
outcomes of meta-analyses. However, most of trials
used the background
diet with
≤ 3%
of total energy derived
from fructose (15-23, 27-33, 35), others trials
did
not
report
the
proportion
of
fructose
in
the
background
(24,
25,
26,
34).
It
was
hard
to
make
sure
the
dose
of
background
fructose
in
every
trial.
Third,
the
data
provided by
Reiser
et
al
(23) must
be interpreted
with
caution.
Although this study
met all of our
inclusion criteria, they choose a low P:S
(polyunsaturated : saturated)
rate of
the fat as the background diet, which might change
the metabolism of fructose
as diets
high in saturated fatty acids can enhance
intestinal fructose absorption (48).
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