Similar a Consumption of Synbiotic Bread Decreases Triacylglycerol and VLDL Levels While Increasing HDL Levels in Serum from Patients with Type-2 Diabetes
Similar a Consumption of Synbiotic Bread Decreases Triacylglycerol and VLDL Levels While Increasing HDL Levels in Serum from Patients with Type-2 Diabetes (20)
Consumption of Synbiotic Bread Decreases Triacylglycerol and VLDL Levels While Increasing HDL Levels in Serum from Patients with Type-2 Diabetes
1. ORIGINAL ARTICLE
Consumption of Synbiotic Bread Decreases Triacylglycerol
and VLDL Levels While Increasing HDL Levels in Serum
from Patients with Type-2 Diabetes
Hossein Shakeri • Haleh Hadaegh • Fatemeh Abedi •
Maryam Tajabadi-Ebrahimi • Navid Mazroii •
Yaser Ghandi • Zatollah Asemi
Received: 11 February 2014 / Accepted: 20 March 2014
Ó AOCS 2014
Abstract To our knowledge, no reports are available
indicating the favorable effects of synbiotic bread con-
sumption on blood lipid profiles among patients with type 2
diabetes mellitus (T2DM). This study was conducted to
evaluate the effects of the daily consumption of synbiotic
bread on blood lipid profiles of patients with T2DM. This
randomized double-blinded controlled clinical trial was
performed with 78 diabetic patients, aged 35–70 years. After
a 2-week run-in period, subjects were randomly assigned to
consume either synbiotic (n = 26), probiotic (n = 26) or
control bread (n = 26) for 8 weeks. The synbiotic bread
contained viable and heat-resistant probiotic Lactobacillus
sporogenes (1 9 108
CFU) and 0.07 g inulin (HPX) as
prebiotic per 1 g. The probiotic bread contained L. sporog-
enes (1 9 108
CFU) per 1 g. Patients were asked to consume
the synbiotic, probiotic and control breads three times a day
in a 40 g package for a total of 120 g/day. Biochemical
measurements including blood lipid profiles were conducted
before and after 8 weeks of intervention. Consumption of the
synbiotic bread, compared to the probiotic and control
breads, led to a significant decrease in serum TAG (P =
0.005), VLDL-C (P = 0.005), TC/HDL-C (P = 0.002) and
a significant increase in serum HDL-C levels (P = 0.01). No
significant effect of synbiotic bread consumption on FPG,
TC, LDL-C and non-HDL-C levels was seen compared to the
probiotic and control breads (P [ 0.05). Trial registry code:
http://www.irct.ir IRCT201311215623N13.
Keywords Synbiotic Á Probiotic Á Lipid profiles Á Type 2
diabetes mellitus
Abbreviations
HDL-C High density lipoprotein-cholesterol
LDL-C Low density lipoprotein-cholesterol
MUFA Monounsaturated fatty acid(s)
PUFA Polyunsaturated fatty acid(s)
SFA Saturated fatty acid(s)
TAG Triacylglycerol(s)
TC Total cholesterol
VLDL-C Very low density lipoprotein-cholesterol
Introduction
Type 2 diabetes mellitus (T2DM), which accounts for
90–95 % of those with diabetes, encompasses individuals
who have insulin resistance and usually have relative
(rather than absolute) insulin deficiency [1]. It has been
estimated that 8.3 % of the adult population in the world
[2] and 8 % in Iran are affected [3]. Due to hyperinsuli-
nemia, insulin resistance and obesity, T2DM is associated
with debilitating consequences including dyslipidemia [4].
Increased lipid profiles among diabetic patients may result
in cardiovascular diseases (CVD)-related morbidity and
mortality [5], fatty liver [6] and kidney failures [7].
H. Shakeri Á F. Abedi Á N. Mazroii Á Y. Ghandi Á Z. Asemi (&)
Research Center for Biochemistry and Nutrition in Metabolic
Diseases, Kashan University of Medical Sciences, Kashan,
Islamic Republic of Iran
e-mail: asemi_r@yahoo.com
H. Hadaegh
Department of Research and Development of Sahar Bread
Company, Tehran, Islamic Republic of Iran
M. Tajabadi-Ebrahimi
Faculty Member of Science Department, Science Faculty,
Islamic Azad University, Tehran Central Branch, Tehran,
Islamic Republic of Iran
123
Lipids
DOI 10.1007/s11745-014-3901-z
2. Weight loss via hypocaloric and low-glycemic index
diets as well as increased physical activity are first-line
treatments in the management of T2DM [8, 9]. Further-
more, other strategies for the management of lipid profiles
in diabetic patients have been suggested including the use
of cholesterol-lowering drugs, antioxidant and mineral
supplementation [10, 11]. Recently, a few studies have also
reported that consumption of probiotics and synbiotics can
result in improved metabolic profiles [12–14]. However,
such effects have mainly been observed in animal models
or non-diabetic patients. In addition, data on the effects of
probiotics and synbiotics on serum lipid profiles are con-
flicting. Intake of a synbiotic containing Lactobacillus
acidophilus, fructo-oligosaccharide, inulin and mannitol
for 8 weeks resulted in decreased serum triglycerides
(TAG), total cholesterol (TC) and LDL-C levels as well as
increased HDL-C concentrations in hypercholesterolemic
pigs [15]. Our previous study with healthy pregnant women
showed decreased serum TAG and VLDL-C levels fol-
lowing consumption of synbiotic food containing heat-
resistant Lactobacillus sporogenes (1 9 107
CFU) and
0.04 g inulin as prebiotic per 1 g after 9 weeks [14].
The beneficial effects of probiotics and synbiotics on
lipid profiles might be explained by the production of short
chain fatty acids (SCFA) [16] as well as carbon disulfide
and methyl acetate [17], assimilation of cholesterol in the
gastrointestinal tract, enzymatic deconjugation of bile acids
[18, 19] and conversion of cholesterol into coprostanol in
the gut [20]. We are unaware of any study evaluating the
effects of daily consumption of probiotic and synbiotic
breads on lipid profiles among patients with T2DM. The
aim of the current study was, therefore, to investigate the
effects of daily consumption of synbiotic bread on lipid
profiles in T2DM patients.
Participants
This randomized, double-blinded, controlled, clinical trial
was conducted in Kashan, Iran, during October 2013–
December 2013. To estimate the required sample size, we
used the appropriate formula, where the type 1 (a) and
type 2 errors (b) were considered as 0.05 and 0.20
(power = 80 %), respectively. In addition, serum HDL-C
levels was defined as the key variable and based on earlier
studies [21], the standard deviation of this variable was
14.16 mg/dL. We considered 11.21 mg/dL as the signifi-
cant difference in mean HDL-C between the two groups.
Therefore, the estimated sample size was 25 subjects in
each group. Diagnosis of T2DM was based on the criteria
of the American Diabetes Association [22]: those with one
of the following criteria were considered as having T2DM:
fasting plasma glucose (FPG) C 126 mg/dL, blood sugar
(BS) 2-h pp C 200 mg/dL and HbA1C C 6.5 %. Individ-
uals with the above-mentioned inclusion criteria were
called in for participation in the study from those that
attended Golabchi Diabetes Clinic affiliated to Kashan
University of Medical Sciences, Kashan, Iran. Subjects
were not included if they were pregnant, using insulin or
vitamin supplements, or had chronic kidney, liver, lung and
chronic or acute inflammatory disease, heart valve disease,
short bowel syndrome or allergies. The study was con-
ducted according to the guidelines laid down in the Dec-
laration of Helsinki. The ethical committee of Kashan
University of Medical Sciences approved the study and
informed written consent was obtained from all
participants.
Study Procedure
To obtain detailed information about the dietary intakes of
study participants, all patients entered into a 2-week run-in
period; during which they were advised to refrain from
taking any other synbiotic and probiotic foods. During the
run-in period, participants were asked to record their
dietary intakes for three non-consecutive days. At the end
of the run-in period, subjects were randomly assigned to
the initial arm of the study to receive either probiotic,
synbiotic or control breads for 8 weeks. Participants were
asked not to alter their routine physical activity or usual
diets and to not consume any synbiotic, probiotic and
fermented products other than those provided for them.
Probiotic, synbiotic or control breads were supplied to
participants every 3 days. Compliance with the con-
sumption of foods was monitored once a week through
phone interviews and by the use of 3-day dietary records
completed in each phase of intervention. The dietary
records were based on estimated values in household
measurements. To obtain nutrient intakes of participants
based on these three-day food diaries in each phase, we
used Nutritionist IV software (First Databank, San Bruno,
CA) modified for Iranian foods.
Assessment of Variables
Anthropometric measurements were performed at baseline
and after 8 weeks of intervention in each arm. Body weight
was measured in an overnight fasting state, without shoes
and in minimal clothing with a digital scale (Seca, Ham-
burg, Germany) to the nearest 0.1 kg. Height was measured
using a non-stretched tape measure (Seca, Hamburg, Ger-
many) to the nearest 0.1 cm. The BMI was calculated as
weight in kg divided by the height in meters squared.
Lipids
123
3. Biochemical Assessment
Fasting blood samples (10 mL) were taken at baseline and
after the 8-week intervention at Kashan reference labo-
ratory after an overnight fast. Fasting plasma glucose
(FPG), serum TAG, TC, HDL-C and LDL-C concentra-
tions were assayed using the standard enzymatic methods
with commercial kits (Parsazmun, Tehran, Iran). Serum
VLDL-C concentration was assessed by photometric
methods in which LDL-C, HDL-C and chylomicrons were
blocked by antibodies and finally the VLDL-C concen-
tration was evaluated by enzymatic measurement and with
available kits (Zistshimi, Tehran, Iran). All inter- and
intra-assay CV for lipid profile measurements were less
than 5 %.
Synbiotic, Probiotic and Control Breads
The synbiotic bread contained a viable and heat-resistant
probiotic, L. sporogenes (1 9 108
CFU) and 0.07 g inulin
(HPX) as prebiotic per 1 g. The probiotic bread containing
L. sporogenes (1 9 108
CFU) per 1 g. The control bread
(the same substance without probiotic bacteria and prebi-
otic inulin) was packed in identical packages and coded by
the producer to guarantee blinding. Patients were asked to
consume the synbiotic, probiotic and control breads three
times a day for a total of 120 g/day. Due to viability against
the high temperature, acidity of the stomach, bile acids and
growth at physiological conditions as well as beneficial
effects on the intestinal environment, stool frequency and
characteristics [23], we selected L. sporogenes over other
Lactobacillus species. The synbiotic, probiotic and control
breads were provided by the Sahar Bread Company, Teh-
ran, Iran.
Statistical Analysis
To ensure the normal distribution of variables, the Kol-
mogorov–Smirnov test were applied. Log transformation
was performed for non-normally distributed variables. The
analyses were done based on the intention-to-treat
approach. Missing values were treated based on the Last-
Observation-Carried-Forward (LOCF) method. LOCF
ignores whether the participant’s condition was improving
or deteriorating at the time of dropout but instead freezes
outcomes at the value observed before dropout (i.e., last
observation). One-way analysis of variance (ANOVA) was
used to detect differences in general characteristics and
dietary intakes between the three groups. To determine
the effect of probiotic, synbiotic and control breads on
lipid profiles, we applied repeated measures analysis of
variance. In these analyses, the treatments (probiotic,
synbiotic and control breads) were regarded as between-
subject factors and time was considered as within-subject
factor. The changes across three groups were compared
using one-way analysis of variance with Bonferoni post-
hoc pair-wise comparisons. To assess if the magnitude of
the change depended on the baseline values, age and
baseline BMI, we conditioned all analyses on baseline
values, age and baseline BMI to avoid potential bias. These
adjustments were done using analysis of covariance
(ANCOVA). All statistical analyses were done using the
Statistical Package for Social Science version 17 (SPSS
Inc., Chicago, IL, USA).
Results
A total of 78 patients (15 males and 63 females) with
T2DM were recruited in the study. After matching for age,
sex, BMI, type and dosage of oral hypoglycemic medica-
tions, and dosage of lowering lipid medications, partici-
pants were randomly assigned to receive either synbiotic
(n = 26) or probiotic (n = 26) or control breads (n = 26)
for 8 weeks. The exclusions in the control bread were two
patients [insulin therapy (n = 1) and supplement therapy
(n = 1)]. Among individuals in the probiotic bread group,
two persons [antibiotic treatment (n = 1) and withdrawal
(n = 1)] and in synbiotic bread group, two persons [with-
drawal (n = 1) and supplement therapy (n = 1)] dropped
out. Finally, 72 participants [synbiotic bread (n = 24),
probiotic bread (n = 24) and control bread (n = 24)]
completed the trial (Fig. 1). Therefore, 24/26 persons of
each group were available for follow-up measures. How-
ever, as the analysis was done based on intention-to-treat
approach, all 78 patients (26 in each group) were included
in the final analysis.
No serious adverse events were reported throughout
the study. Comparing the anthropometric measures at
baseline and after intervention, we found no significant
differences in weight and BMI between the three groups
(Table 1).
No statistically significant difference was seen between
the three groups in dietary intake of energy, carbohydrate,
protein, fat, saturated fatty acids (SFA), polyunsaturated
fatty acids (PUFA), monounsaturated fatty acids (MUFA),
cholesterol or total dietary fiber (TDF) (Table 2).
Consumption of the synbiotic bread, compared to the
probiotic and control breads, led to a significant decrease in
serum TAG (-26.7 ± 60.3 vs. -31.6 ± 80.0 and
33.0 ± 85.9 mg/dL, respectively, P = 0.005), VLDL-C
(-5.3 ± 12.1 vs. -6.3 ± 16.0 and 6.6 ± 17.2 mg/dL,
Lipids
123
4. respectively, P = 0.005), TC/HDL-C (-0.5 ± 0.8 vs.
-0.6 ± 1.1 and 4.1 ± 1.1, respectively, P = 0.002) and a
significant increase in serum HDL-C levels (2.2 ± 6.8 vs.
2.2 ± 8.0 and -3.1 ± 7.5 mg/dL, respectively, P = 0.01)
(Table 3). No significant effect of synbiotic bread con-
sumption on FPG, TC, LDL-C and non-HDL-C levels was
seen. In addition, in a pair-wise comparison between
synbiotic and probiotic groups, no significant differences
was seen.
When we adjusted the analysis for baseline values, the
above-mentioned findings remained significant, except for
TC (P = 0.01), HDL-C (P = 0.07) and non-HDL-C
(P = 0.003) (Table 4). Adjustment for age and baseline
BMI did not affect our findings.
Lost to follow-up (n=2)
Insulin therapy (n=1)
Supplement use (n=1)
Analyzed (n=26)
Follow-upAnalysis
Lost to follow-up (n=2)
Antibiotic use (n=1)
Withdraw (n=1)
Lost to follow-up (n=2)
Withdraw (n=1)
Supplement use (n=1)
Analyzed (n=26) Analyzed (n=26)
Randomized (n=78)
Assessed for eligibility (n= 100)
Excluded (n=22)
Not living in Kashan (n=6)
Taking excluded insulin therapy
(n=16)
EnrollmentAllocation
Allocated to probiotic bread
(n=26)
Allocated to synbiotic bread
(n=26)
Allocated to control bread
(n=26)
Fig. 1 Summary of patient
flow diagram
Table 1 General
characteristics of study
participants
a
P values were computed by
the ANOVA test
b
Values are presented as
means ± SD
Control bread
(n = 26)
Probiotic bread
(n = 26)
Synbiotic bread
(n = 26)
P valuea
Age (years) 53.1 ± 7.5b
52.3 ± 8.2 52.3 ± 10.8 0.93
Height (cm) 158.5 ± 7.7 159.1 ± 8.8 161.8 ± 10.6 0.37
Weight at study baseline (kg) 76.9 ± 12.3 74.4 ± 14.3 80.8 ± 15.5 0.26
Weight at end-of-trial (kg) 76.9 ± 12.1 74.2 ± 14.4 80.8 ± 15.6 0.24
Weight change (kg) -0.05 ± 1.6 -0.2 ± 1.4 0.03 ± 1.9 0.92
BMI at study baseline (kg/m2
) 30.6 ± 4.1 29.5 ± 5.7 30.9 ± 6.0 0.57
BMI at end-of-trial (kg/m2
) 30.6 ± 4.1 29.4 ± 5.9 30.9 ± 5.9 0.56
BMI change (kg/m2
) -0.02 ± 0.6 -0.04 ± 0.6 0.02 ± 0.8 0.97
Metformin use (number/day) 2.1 ± 0.9 2.0 ± 1.1 2.1 ± 1.2 0.92
Glibenclamide use (number/day) 2.1 ± 0.8 1.9 ± 1.1 2.0 ± 1.3 0.74
Gemfibrozil use (number/day) 0.1 ± 0.4 0.1 ± 0.3 0.1 ± 0.3 0.97
Atorvastatin use (number/day) 0.5 ± 0.6 0.5 ± 0.5 0.5 ± 0.5 0.90
Lipids
123
5. However, when we carried out analysis without the
intention-to-treat approach (excluding subjects with insulin
and supplement therapy, antibiotic use and withdraw), no
significant change was seen in our findings.
Discussion
The current study demonstrated that consumption of syn-
biotic bread for 8 weeks among diabetic patients has ben-
eficial effects on serum TAG, VLDL-C, TC/HDL-C and
HDL-C levels; however, no change was observed in FPG,
serum TC, LDL-C and non-HDL-C levels. To the best of
our knowledge, this is the first study to examine the effect
of synbiotic and probiotic breads on lipid profiles of dia-
betic patients.
Patients with T2DM are susceptible to metabolic
complications and dyslipidemia [5]. In line with our study,
Liong et al. [15] reported decreased serum TAG, TC and
LDL-C levels as well as increased concentrations of HDL-
C in hypercholesterolemic pigs after 8 weeks following
the consumption of a synbiotic food containing L. aci-
dophilus, fructo-oligosaccharide, inulin and mannitol.
Furthermore, our previous study involving healthy preg-
nant women showed decreased serum TAG and VLDL-C
after consumption of synbiotic food containing heat-
resistant L. sporogenes (1 9 107
CFU) and 0.04 g inulin
as a prebiotic per 1 g for 9 weeks [14]. The same results
were seen among pregnant women who received probiotic
yogurt containing L. acidophilus LA5 and Bifidobacterium
animalis BB12 with a total of min 1 9 107
CFU after
9 weeks [24] and among young healthy subjects who
received a diet with inulin-enriched pasta after 5 weeks
[25]. In contrast, some investigators did not find a sig-
nificant effect of synbiotic and probiotic supplementation
on lipid profiles. For instance, our previous study among
patients with T2DM did not show any significant differ-
ence in lipid profiles following the consumption of a
synbiotic food containing L. sporogenes (1 9 107
CFU)
and 0.04 g inulin as prebiotic per 1 g after 6 weeks [21].
Consumption of Kefir did not show any effect on serum
lipid profiles among hyperlipidemic men after 4 weeks
[26]. Similar findings were seen with consumption of a
combination of L. acidophilus and B. animalis among
healthy women for 4 weeks [27].
The TAG and VLDL-C decreasing effects as well as the
HDL-C increasing effect of the synbiotic and probiotic
breads may be due to SCFA production especially propi-
onate, which in turn could inhibit the synthesis of fatty
acids in the liver, thereby decreasing the TAG and VLDL-
C secretion rate and serum TAG and VLDL-C levels [28].
Furthermore, inulin has been shown to be a determining
factor in decreased expression of the enzymes involved in
fatty acid synthesis [29] and suppressed gene expression of
lipogenic enzymes [30]. Synbiotics and probiotics may also
affect serum lipid profiles through their immune-modula-
tory effects [31], TLR4 signaling and pro-inflammatory
cytokines [32].
Limitations
Several limitations must be considered in the interpreta-
tion of our findings. Firstly, we did not assess the effects
of synbiotic and probiotic breads on fecal SCFA. Sec-
ondly, we did not assess the effects of synbiotic and
probiotic breads on inflammatory factors such as TNF-a
and IL6.
In conclusion, consumption of the synbiotic bread for
8 weeks among patients with T2DM resulted in a signifi-
cant decrease in serum TAG, VLDL-C, TC/HDL-C and a
significant rise in serum HDL-C levels compared with
probiotic and control breads, but did not affect FPG, TC,
LDL-C and non-HDL-C levels. Further studies are needed
to determination the mechanisms responsible for these
effects.
Table 2 Dietary intakes of
study participants throughout
the study
SFA saturated fatty acids, PUFA
polyunsaturated fatty acids,
MUFA monounsaturated fatty
acids, TDF total dietary fiber
a
P values were computed by
the ANOVA test
b
Values are presented as
means ± SD
Control bread
(n = 26)
Probiotic bread
(n = 26)
Synbiotic bread
(n = 26)
P valuea
Energy (kcal/day) 2,202 ± 234b
2,197 ± 294 2,281 ± 226 0.41
Carbohydrates (g/day) 246.7 ± 50.7 261.8 ± 46.9 273.5 ± 41.9 0.12
Protein (g/day) 72.0 ± 10.8 73.9 ± 10.9 76.8 ± 11.7 0.30
Fat (g/day) 106.2 ± 20.1 98.7 ± 19.9 101.8 ± 21.2 0.41
SFA (g/day) 23.1 ± 5.7 22.3 ± 4.7 24.3 ± 5.3 0.39
PUFA (g/day) 45.8 ± 12.5 42.8 ± 12.7 39.6 ± 13.1 0.22
MUFA (g/day) 27.5 ± 7.3 26.5 ± 7.4 30.2 ± 11.1 0.29
Cholesterol (mg/day) 179.4 ± 98.3 179.5 ± 81.1 186.9 ± 84.9 0.94
TDF (g/day) 16.0 ± 3.4 16.7 ± 4.6 17.6 ± 3.9 0.35
Lipids
123
6. Acknowledgments The present study was supported by a Grant
(No. 92107) from the Vice-Chancellor for Research, KUMS, Kashan,
Iran. The authors would like to thank the staff of Gholabchi Clinic
(Kashan, Iran) for their assistance in this project. We are grateful to
the Research and Development Department of Sahar Bread Company,
Tehran, Iran that provided probiotic and synbiotic products for the
present study. Furthermore, we are grateful to the Research and
Development Department of Tak Gene Zist Company, Tehran, Iran
that provided Lactobacillus sporogenes for this study.
Conflict of interest None of the authors had any personal or
financial conflict of interest.
References
1. American Diabetes Association (2014) Diagnosis and classifica-
tion of diabetes mellitus. Diabetes Care 37(Suppl 1):S81–S90
2. Ruggiero L, Castillo A, Quinn L, Hochwert M (2012) Translation
of the diabetes prevention program’s lifestyle intervention: role
of community health workers. Curr Diab Rep 12:127–137
Table3Theeffectofdailyconsumptionofprobioticandsynbioticbreadsonlipidprofiles
Controlbread(n=26)Probioticbread(n=26)Synbioticbread(n=26)Pvaluea
Week0Week8ChangeWeek0Week8ChangeWeek0Week8ChangeTimeGroupTime9group
FPG(mg/dL)168.1±78.9b
168.4±86.10.3±76.4129.7±37.0123.7±38.9-6.0±38.3142.7±58.7127.1±39.7-15.6±52.40.280.010.60
TAG(mg/dL)144.6±67.0177.6±87.933.0±85.9148.7±68.4117.1±50.8-31.6±80.0*165.5±68.2138.8±57.7-26.7±60.3*0.330.180.005
VLDL-C(mg/dL)28.9±13.435.5±17.66.6±17.229.7±13.723.4±10.2-6.3±16.0*33.1±13.627.8±11.5-5.3±12.1*0.330.180.005
TC(mg/dL)179.6±43.5179.1±35.3-0.5±34.8170.4±38.0154.4±30.5-16.0±43.8155.5±35.3145.2±38.9-10.3±42.20.050.0050.38
LDL-C(mg/dL)104.9±41.8100.8±30.7-4.1±39.797.5±34.885.7±26.2-11.8±37.982.8±28.775.6±30.0-7.2±34.90.070.0080.75
HDL-C(mg/dL)45.8±8.142.7±7.7-3.1±7.543.1±10.245.3±10.52.2±8.0*39.6±8.941.8±9.52.2±6.8*0.610.220.01
TC/HDL-C4.0±1.34.3±1.20.3±0.94.1±1.13.5±0.7-0.6±1.1*4.0±1.03.5±0.8-0.5±0.8*0.010.220.002
Non-HDL-C
(mg/dL)
133.9±42.4136.4±34.92.5±34.2127.3±35.7109.2±27.0-18.1±41.8115.9±33.7103.4±35.5-12.5±38.30.030.0090.13
FPGfastingplasmaglucose,TAGtriacylglycerols,TCtotalcholesterol,HDL-Chighdensitylipoprotein-cholesterol,VLDL-Cverylowdensitylipoprotein-cholesterol,LDL-Clowdensity
lipoprotein-cholesterol
*Significantdifferencewiththecontrolgroup
a
Pvaluesrepresentthetime9groupinteraction(computedbyanalysisoftherepeatedmeasuresANOVA)
b
Valuesarepresentedasmeans±SD
Table 4 Adjusted changes in lipid profiles in diabetic patients that
received either probiotic or synbiotic or control breads
Control
bread
(n = 26)
Probiotic
bread
(n = 26)
Synbiotic
bread
(n = 26)
P valuea
FPG (mg/dL)
Model 1b
10.5 ± 10.1d
-14.2 ± 10.0 -17.6 ± 9.9 0.10
Model 2c
0.2 ± 11.4 -6.4 ± 11.5 -15.0 ± 11.4 0.64
TAG (mg/dL)
Model 1 27.7 ± 12.4 -34.3 ± 12.4 -18.7 ± 12.5 0.002
Model 2 33.9 ± 15.0 -33.0 ± 15.1 -26.3 ± 15.0 0.004
VLDL-C (mg/dL)
Model 1 5.5 ± 2.5 -6.9 ± 2.5 -3.7 ± 2.5 0.002
Model 2 6.8 ± 3.0 -6.6 ± 3.0 -5.3 ± 3.0 0.004
TC (mg/dL)
Model 1 6.5 ± 6.4 -14.8 ± 6.3 -18.6 ± 6.4 0.01
Model 2 -0.2 ± 8.0 -16.6 ± 8.0 -10.1 ± 8.0 0.35
LDL-C (mg/dL)
Model 1 3.1 ± 5.5 -10.1 ± 5.4 -16.1 ± 5.5 0.05
Model 2 -3.9 ± 7.4 -12.5 ± 7.5 -6.7 ± 7.4 0.70
HDL-C (mg/dL)
Model 1 -2.1 ± 1.4 2.2 ± 1.4 1.2 ± 1.4 0.07
Model 2 -3.1 ± 1.4 2.5 ± 1.4 1.9 ± 1.4 0.01
TC/HDL-C
Model 1 0.3 ± 0.1 -0.6 ± 0.1 -0.5 ± 0.1 0.001
Model 2 0.3 ± 0.2 -0.6 ± 0.2 -0.5 ± 0.2 0.001
Non-HDL-C (mg/dL)
Model 1 7.7 ± 5.9 -17.1 ± 5.8 -18.8 ± 5.9 0.003
Model 2 2.9 ± 7.5 -19.1 ± 7.5 -11.9 ± 7.5 0.11
FPG fasting plasma glucose, TAG triacylglycerols, TC total cholesterol,
HDL-C high density lipoprotein-cholesterol, VLDL-C very low density
lipoprotein-cholesterol, LDL-C low density lipoprotein-cholesterol
a
P values were computed by ANCOVA test
b
Adjusted for baseline values
c
Adjusted for age and baseline BMI
d
Values are presented as means ± SE
Lipids
123
7. 3. Haghdoost AA, Rezazadeh-Kermani M, Sadghirad B, Baradaran
HR (2009) Prevalence of type 2 diabetes in the Islamic Republic
of Iran: systematic review and meta-analysis. East Mediterr
Health J 15:591–599
4. Johnson M, Krosnick A, Carson P, McDade AM, Laraway K
(1998) A retrospective chart review of uncontrolled use of met-
formin as an add-on therapy in type 2 diabetes. Clin Ther
20:691–698
5. Krentz AJ (2003) Lipoprotein abnormalities and their conse-
quences for patients with type 2 diabetes. Diabetes Obes Metab
5(Suppl 1):S19–S27
6. Arca M, Pigna G, Favoccia C (2012) Mechanisms of diabetic
dyslipidemia: relevance for atherogenesis. Curr Vasc Pharmacol
10:684–686
7. Yamashita T, Makino H, Nakatani R, Ohata Y, Miyamoto Y,
Kishimoto I (2013) Renal insufficiency without albuminuria is
associated with peripheral artery atherosclerosis and lipid
metabolism disorders in patients with type 2 diabetes. J Atheros-
cler Thromb 20:790–797
8. Juanola-Falgarona M, Ibarrola-Jurado N, Salas-Salvado J, Ra-
bassa-Soler A, Bullo M (2013) Design and methods of the
GLYNDIET study; assessing the role of glycemic index on
weight loss and metabolic risk markers. Nutr Hosp 28:382–390
9. Ajala O, English P, Pinkney J (2013) Systematic review and
meta-analysis of different dietary approaches to the management
of type 2 diabetes. Am J Clin Nutr 97:505–516
10. Masana L (2013) Pitavastatin in cardiometabolic disease: thera-
peutic profile. Cardiovasc Diabetol 12(Suppl 1):S2
11. Farvid MS, Siassi F, Jalali M, Hosseini M, Saadat N (2004) The
impact of vitamin and/or mineral supplementation on lipid pro-
files in type 2 diabetes. Diabetes Res Clin Pract 65:21–28
12. Worthley DL, Le Leu RK, Whitehall VL, Conlon M, Christo-
phersen C, Belobrajdic D et al (2009) A human, double-blind,
placebo-controlled, crossover trial of prebiotic, probiotic, and
synbiotic supplementation: effects on luminal, inflammatory,
epigenetic, and epithelial biomarkers of colorectal cancer. Am J
Clin Nutr 90:578–586
13. Ndagijimana M, Laghi L, Vitali B, Placucci G, Brigidi P,
Guerzoni ME (2009) Effect of a synbiotic food consumption on
human gut metabolic profiles evaluated by (1)H nuclear magnetic
resonance spectroscopy. Int J Food Microbiol 134:147–153
14. Taghizadeh M, Hashemi T, Shakeri H, Abedi F, Sabihi SS,
Alizadeh SA et al (2014) Synbiotic food consumption reduces
levels of triacylglycerols and VLDL, but not cholesterol, LDL, or
HDL in plasma from pregnant women. Lipids 49:155–161
15. Liong MT, Dunshea FR, Shah NP (2007) Effects of a synbiotic
containing Lactobacillus acidophilus ATCC 4962 on plasma lipid
profiles and morphology of erythrocytes in hypercholesterolae-
mic pigs on high- and low-fat diets. Br J Nutr 98:736–744
16. Pereira DI, Gibson GR (2002) Effects of consumption of probi-
otics and prebiotics on serum lipid levels in humans. Crit Rev
Biochem Mol Biol 37:259–281
17. Vitali B, Ndagijimana M, Maccaferri S, Biagi E, Guerzoni ME,
Brigidi P (2012) An in vitro evaluation of the effect of probiotics
and prebiotics on the metabolic profile of human microbiota.
Anaerobe 18:386–391
18. Lin MY, Chang FJ (2000) Antioxidative effect of intestinal
bacteria Bifidobacterium longum ATCC 15708 and Lactobacillus
acidophilus ATCC 4356. Dig Dis Sci 45:1617–1622
19. Lambert JM, Bongers RS, de Vos WM, Kleerebezem M (2008)
Functional analysis of four bile salt hydrolase and penicillin
acylase family members in Lactobacillus plantarum WCFS1.
Appl Environ Microbiol 74:4719–4726
20. Lye HS, Rusul G, Liong MT (2010) Removal of cholesterol by
lactobacilli via incorporation and conversion to coprostanol.
J Dairy Sci 93:1383–1392
21. Asemi Z, Khorrami-Rad A, Alizadeh SA, Shakeri H, Esmaill-
zadeh A (2014) Effects of synbiotic food consumption on meta-
bolic status of diabetic patients: a double-blind randomized cross-
over controlled clinical trial. Clin Nutr 33:198–203
22. American Diabetes Association (2012) Diagnosis and classifica-
tion of diabetes mellitus. Diabetes Care 35 Suppl 1:S64–S71
23. Endres JR, Clewell A, Jade KA, Farber T, Hauswirth J, Schauss
AG (2009) Safety assessment of a proprietary preparation of a
novel probiotic, Bacillus coagulans, as a food ingredient. Food
Chem Toxicol 47:1231–1238
24. Asemi Z, Samimi M, Tabasi Z, Talebian P, Azarbad Z, Hydar-
zadeh Z et al (2012) Effect of daily consumption of probiotic
yoghurt on lipid profiles in pregnant women: a randomized
controlled clinical trial. J Matern Fetal Neonatal Med
25:1552–1556
25. Russo F, Riezzo G, Chiloiro M, De Michele G, Chimienti G,
Marconi E et al (2010) Metabolic effects of a diet with inulin-
enriched pasta in healthy young volunteers. Curr Pharm Des
16:825–831
26. St-Onge MP, Farnworth ER, Savard T, Chabot D, Mafu A, Jones
PJ (2002) Kefir consumption does not alter plasma lipid levels or
cholesterol fractional synthesis rates relative to milk in hyper-
lipidemic men: a randomized controlled trial [IS-
RCTN10820810]. BMC Complement Altern Med 2:1
27. Savard P, Lamarche B, Paradis ME, Thiboutot H, Laurin E, Roy
D (2011) Impact of Bifidobacterium animalis subsp. lactis BB-12
and, Lactobacillus acidophilus LA-5-containing yoghurt, on fecal
bacterial counts of healthy adults. Int J Food Microbiol
149:50–57
28. Trautwein EA, Rieckhoff D, Erbersdobler HF (1998) Dietary
inulin lowers plasma cholesterol and triacylglycerol and alters
biliary bile acid profile in hamsters. J Nutr 128:1937–1943
29. Williams CM (1999) Effects of inulin on lipid parameters in
humans. J Nutr 129:1471S–1473S
30. Delzenne NM, Kok N (2001) Effects of fructans-type prebiotics
on lipid metabolism. Am J Clin Nutr 73:456S–458S
31. Konstantinov SR, Smidt H, de Vos WM, Bruijns SC, Singh SK,
Valence F et al (2008) S layer protein A of Lactobacillus aci-
dophilus NCFM regulates immature dendritic cell and T cell
functions. Proc Natl Acad Sci USA 105:19474–19479
32. Ouwehand AC, Tiihonen K, Saarinen M, Putaala H, Rautonen N
(2009) Influence of a combination of Lactobacillus acidophilus
NCFM and lactitol on healthy elderly: intestinal and immune
parameters. Br J Nutr 101:367–375
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