Probiotic yogurt improves antioxidant status in type 2 diabetic patients.
ABSTRACT Oxidative stress plays a major role in the pathogenesis and progression of diabetes. Among various functional foods with an antioxidant effect, probiotic foods have been reported to repress oxidative stress. The objective of this clinical trial was to assess the effects of probiotic and conventional yogurt on blood glucose and antioxidant status in type 2 diabetic patients.
Sixty-four patients with type 2 diabetes mellitus, 30 to 60 y old, were assigned to two groups in this randomized, double-blind, controlled clinical trial. The patients in the intervention group consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 and those in the control group consumed 300 g/d of conventional yogurt for 6 wk. Fasting blood samples, 24-h dietary recalls, and anthropometric measurements were collected at the baseline and at the end of the trial.
Probiotic yogurt significantly decreased fasting blood glucose (P < 0.01) and hemoglobin A1c (P < 0.05) and increased erythrocyte superoxide dismutase and glutathione peroxidase activities and total antioxidant status (P < 0.05) compared with the control group. In addition, the serum malondialdehyde concentration significantly decreased compared with the baseline value in both groups (P < 0.05). No significant changes from baseline were shown in insulin concentration and erythrocyte catalase activity within either group (P > 0.05).
The consumption of probiotic yogurt improved fasting blood glucose and antioxidant status in type 2 diabetic patients. These results suggest that probiotic yogurt is a promising agent for diabetes management.
- SourceAvailable from: Emeline Roux[Show abstract] [Hide abstract]
ABSTRACT: Besides their basic nutritional role, dietary proteins contain bioactive peptides which are encrypted in their sequence and may modulate different body functions such as digestive, cardiovascular, immune and nervous systems, and therefore contribute in maintaining consumer health. Currently, milk proteins are considered to be the major source of bioactive peptides. The occurrence of these peptides has already been reported in fermented milk products such as yogurt, sour milk or kefir and some of them have been shown to confer health benefits. This review focuses on different strategies that could be employed to enhance the production of bioactive peptides from the milk proteins that will be consequently used to functionalize the fermented milk products. Three types of strategies are developed. The first exploits the proteolytic system of lactic acid bacteria (LAB) or food grade enzymes or combination of both to release the functional peptides from the milk proteins directly in the fermented milk products. The second concerns the supplementation of the fermented milk products with the bioactive peptides obtained outside of the product through the hydrolysis of the purified proteins by the same enzyme sources. Finally, the last consists in the production of the bioactive peptides, initially identified from the milk-proteins, by microorganisms using recombinant DNA technology.Food Research International 09/2014; 63(partA):71-80. · 3.05 Impact Factor
- Journal of food and nutrition research 01/2014; 2(8):491-98. · 0.60 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Rats fed high fat diets have alterations of their intestinal microbiota, gut barrier function, circulating lipopolysaccharide (LPS) levels and biomarkers of oxidative stress, inflammation, and glucose/insulin metabolism, resulting in a higher risk of type-2 diabetes. These deleterious effects are prevented by antibiotics or prebiotics. The aim of this study was to determine whether the administration of a synbiotic improves metabolic alterations and low grade inflammation in obese subjects. A randomized, double-blind, controlled clinical trial (www.ClinicalTrials.gov, Access Number NCT01235026) was carried out in 40 obese patients. Subjects were distributed in two groups to receive 8g oligofructose + 1 g of lyophilized Bifidobacterium lactis Bb12 (1010 CFU/g) or 9g maltodextrin as placebo, twice a day for six weeks. Body composition, blood lipids, antioxidant capacity of plasma, biomarkers of inflammation (usCRP, IL-6) and LPS exposure (LPS-Binding Protein, LBP, and sCD14), areas under curves of glycemia and insulinemia and fecal microbiota (qPCR) were quantified at baseline and after treatment. 38 subjects (34.8 ± 9.2y; BMI: 36.7 ± 5.3 kg.m-2) completed the study. A positive correlation was observed at baseline between usCRP, IL-6, LBP, sCD14 and the percentage of body fat; correlations also existed between usCRP, IL-6 and LBP values while sCD14 only correlated with IL-6. Compared with placebo, the administration of synbiotic increased the fecal levels of Bifidobacterium spp. but did not affect body composition, lipid profile, antioxidant status and areas under curves of glycemia and insulinemia, nor the plasma concentrations of usCRP, IL-6 and LBP. Plasma concentrations of sCD14 were significantly lower after treatment in the symbiotic group compared with the placebo 3 group (5.98 μg/ml [5.01-6.96] vs. 7.26 [6.34-8.09] μg/ml (Means [CI95%), respectively; p=0.043). The synbiotic increased fecal bifidobacteria in obese subjects without improvement the biochemical, inflammatory and metabolic markers; more studies are required to elucidate the role of the symbiotic on plasma sCD14.08/2014; 2(2):491-498.
Applied nutritional investigation
Probiotic yogurt improves antioxidant status in type 2 diabetic patients
Hanie S. Ejtahed M.Sc.a, Javad Mohtadi-Nia Ph.D.a, Aziz Homayouni-Rad Ph.D.a,*,
Mitra Niafar M.D., Ph.D.b, Mohammad Asghari-Jafarabadi Ph.D.a, Vahid Mofid M.Sc.c
aFaculty of Health and Nutrition, Tabriz University of Medical Sciences, Tabriz, Iran
bFaculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
cIran Dairy Industries Co., Tehran, Iran
a r t i c l e i n f o
Received 16 March 2011
Accepted 19 August 2011
Type 2 diabetes
Antioxidant enzyme activity
Randomized clinical trial
a b s t r a c t
Objective: Oxidative stress plays a major role in the pathogenesis and progression of diabetes.
Among various functional foods with an antioxidant effect, probiotic foods have been reported to
repress oxidative stress. The objective of this clinical trial was to assess the effects of probiotic and
conventional yogurt on blood glucose and antioxidant status in type 2 diabetic patients.
Methods: Sixty-four patients with type 2 diabetes mellitus, 30 to 60 y old, were assigned to two
groups in this randomized, double-blind, controlled clinical trial. The patients in the intervention
group consumed 300 g/d of probiotic yogurt containing Lactobacillus acidophilus La5 and Bifido-
bacterium lactis Bb12 and those in the control group consumed 300 g/d of conventional yogurt for
6 wk. Fasting blood samples, 24-h dietary recalls, and anthropometric measurements were
collected at the baseline and at the end of the trial.
Results: Probiotic yogurt significantly decreased fasting blood glucose (P < 0.01) and hemoglobin
A1c (P < 0.05) and increased erythrocyte superoxide dismutase and glutathione peroxidase
activities and total antioxidant status (P < 0.05) compared with the control group. In addition, the
serum malondialdehyde concentration significantly decreased compared with the baseline value in
both groups (P < 0.05). No significant changes from baseline were shown in insulin concentration
and erythrocyte catalase activity within either group (P > 0.05).
Conclusion: The consumption of probiotic yogurt improved fasting blood glucose and antioxidant
status in type 2 diabetic patients. These results suggest that probiotic yogurt is a promising agent
for diabetes management.
? 2012 Elsevier Inc. All rights reserved.
Type 2 diabetes mellitus (T2DM) has rapidly increased in the
world during the past few decades. Experimental and clinical
evidence has suggested that oxidative stress plays a major role
in the pathogenesis and progression of diabetes and its
complications [1–3]. Diabetes is usually accompanied by an
increased production of free radicals and impaired antioxidant
defenses [2,4]. These conditions can lead to cellular organelle
damage, the dysfunction of enzymes, an impairment of the
binding of paraoxonase-1 to high-density lipoprotein and
protection against lipid peroxidation, and the development of
insulin resistance and may explain the presence of inflamma-
tion in T2DM [1,2,4–6].
Probiotics are live micro-organisms that, when administered
in adequate amounts, confer health benefits on the host [7–9].
The consumption of probiotics have been shown to provide
measurable health benefits, including the prevention and/or
management of diarrhea, constipation, urinary tract infections,
lactose intolerance, allergies, hepatic disease, inflammatory
bowel disease, and diabetes mellitus. Certain species of bifido-
bacteria and lactobacilli used as probiotics can help balance
intestinal microflora [10–13].
Studies have shown that special strains of lactic acid bacteria
have antioxidant properties [14,15]. The antioxidative mecha-
nisms of probiotics could be assigned to reactive oxygen species
scavenging, metal ion chelation, enzyme inhibition, and the
reduction activity and inhibition of ascorbate autoxidation .
In healthy persons, the consumption of goat milk fermented with
The present study was supported by grant 5/4/3229 from the Vice-Chancellor
for Research of Tabriz University of Medical Sciences, Iran.
* Corresponding author. Tel.: þ98-411-335-7581; fax: þ98-411-334-0634.
E-mail address: Homayounia@tbzmed.ac.ir (A. Homayouni-Rad).
0899-9007/$ - see front matter ? 2012 Elsevier Inc. All rights reserved.
Contents lists available at ScienceDirect
journal homepage: www.nutritionjrnl.com
Nutrition 28 (2012) 539–543
Lactobacillus fermentum ME-3 has been shown to increase total
antioxidative status (TAS) and decrease markers of oxidative
stress [16,17]. The antioxidative properties of other probiotic
strains have also been reported in healthy persons [18,19].
Studies using animal models of diabetes have also shown that
Lactobacillus acidophilus and Lactobacillus casei attenuate oxida-
tive stress and have antidiabetic effects [20,21].
Alterations in gut microbiota composition have recently been
documented in patients with T2DM, providing a target for pro-
biotic intervention . Modification of gut microflora by pro-
biotics may be seen as a novel means of regulating glucose
metabolism and improving oxidative stress in T2DM. Thus, in
this controlled trial, we tested the hypothesis that the con-
sumption of probiotic yogurt containing L. acidophilus La5 and
Bifidobacterium lactis Bb12 would improve blood glucose and
antioxidant status in patients with T2DM.
Materials and methods
Sixty-four patients with T2DM 30 to 60 y old with a body mass index (BMI)
lower than 35 kg/m2were recruited for this study from the endocrinology clinic
of Sina Hospital in Tabriz, Iran. Recruitment was done by telephone and adver-
tisements. All patients had been diagnosed with T2DM for at least 1 y. Exclusion
criteria were smoking; the presence of kidney, liver, or inflammatory intestinal
disease, thyroid disorders, immunodeficiency diseases, or lactose intolerance;
required insulin injections; use of nutritional supplements within the previous
3 wk of testing; use of cholesterol-lowering medication, estrogen, progesterone,
or diuretics; pregnancy or breast-feeding; and consuming probiotic yogurtor any
other probiotic products within the previous 2 mo of testing.
The sample size was determined based on the primary information obtained
from the study by Chamari et al.  for catalase (CAT). For an a value equal to
0.05 and a power of 80%, the sample size was computed as 21.788 (z22) per
group . This number was increased to 32 per group to accommodate the
anticipated dropout rate.
Study design and measurements
The present study was a double-blinded, randomized controlled clinical trial
in which subjects were randomly assigned to the probiotic (intervention) or
conventional (control) yogurt group using a block randomization procedure with
matched subjects in each block based on sex and age. The allocation of the
intervention or control group was concealed from the researchers and the pro-
biotic and conventional yogurt containers had an identical appearance. The
yogurt containers had no labeled information about the type of yogurt inside.
Therefore, neither the subjects nor the investigators were aware of the treatment
assignments in this double-blinded study. Each group consisted of 32 patients.
One week before the beginning of the trial, all patients refrained from eating
yogurt or any other fermented foods. Over 6 wk, the probiotic and conventional
groups consumed 300 g/d of probiotic and conventional yogurt, respectively. All
patients were asked, throughout the 6-wk trial, to maintain their usual dietary
habits and lifestyle and to avoid consuming any yogurt other than that provided
to them by the researchers and any other fermented foods. The patients were
instructed to keep the yogurt under refrigeration and to avoid any changes in
medication, if possible.
Arrangementswere made sothat the patients would receivea 1-wk supplyof
their probiotic or conventional yogurts every week. Compliance with the yogurt
consumption guidelines was monitored by telephone interviews once a week.
Information on food consumption, anthropometric measurements, and
fasting blood samples were collected at the beginning and at the end of the trial.
Nutrient intakes during 3 d were estimated using a 24-h dietary recall at the
beginning and at the end of the study. Three-day averages of macro- and
micronutrient intakes were analyzed by Nutritionist 4 software (First Databank,
Hearst Corp, San Bruno, CA, USA).
Anthropometric measurements were recorded by trained personnel. Body
weights were measured using a scale (Seca, Hamburg, Germany) with 0.1-kg
accuracy without shoes and with minimum clothing. Heights were measured
using a stadiometer (Seca) with 0.1-cm accuracy without shoes. BMI was calcu-
lated by dividing body weight (kilograms) by height (meters) squared.
A blood sample was drawn for each patient from the antecubital vein in the
arm after a 12-h overnight fast. The serum samples were separated from whole
blood by centrifugation at 3500 rpm for 10 min (Avanti J-25, Beckman, Brea, CA,
USA). The serum and whole blood samples were frozen immediately at ?70?C
until the assay. Blood samples were analyzed at the Drug Applied Research
Center (Tabriz University of Medical Sciences, Tabriz, Iran). Fasting blood glucose
was measured using the standard enzymatic method with a Parsazmun kit
(Karaj, Iran). Glycated hemoglobin (HbA1c) was measured in the whole blood by
cation exchange chromatography with a NycoCard HbA1c kit (Oslo, Norway).
Insulin concentration was determined by a chemiluminescent immunoassay
using a Liaison analyzer (DiaSorin, Salluggia, Italy). Erythrocyte superoxide dis-
mutase (SOD) activity was measured spectrophotometrically using a Ransod kit
(Randox Laboratories, Crumlin, UK) . Erythrocyte glutathione peroxidase
(GPx) activity was measured using the spectrophotometric technique and
a Ransel kit (Randox Laboratories) according to the method described by Paglia
and Valentine . Erythrocyte CATactivity was measured by the method of Aebi
. Serum total antioxidant capacity was determined using a Randox TAS kit
(Randox Laboratories) . Serum malondialdehyde (MDA) concentration was
determined using the thiobarbituric acid method described by Bilici et al. .
The present study was conducted according to the guidelines laid down in
the Declaration of Helsinki and all procedures involving human persons were
approved by the ethics committee at Tabriz University of Medical Sciences (no.
897). Written informed consent was obtained from all patients (the trial has been
registered in the Iranian Registry of Clinical Trials, available at: http://www.irct.ir,
identifier: IRCT 138903223533N1).
Streptococcus thermophilus. The probiotic yogurt was also enriched with B. lactis
Bb12 and L. acidophilus La5 (Chr. Hansen, Hoersholm, Denmark) as Direct Vat Set
cultures. The yogurts were produced weekly and distributed to the participants.
Probiotic yogurts were sampled 1 d after manufacture (time of distribution)
and microbiologicallyanalyzedeveryweek. Samples were refrigerated at 4?, with
subsequent analyzing on day 7 of storage. MRS-bile agar medium was used for
the differential enumeration of mixed probiotic bacteria in presence of yogurt
bacteria . All the samples were incubated at 37?C for 72 h under aerobic and
anaerobic conditions. All experiments were performed in triplicate. Counts of L.
acidophilus were achieved at the aerobic condition and viable counts of B. lactis
were selectively achieved using the subtractive enumeration method .
Microbiological analyses of the probiotic yogurts showed that the average
colony counts of L. acidophilus La5 and B. lactis Bb12 on day 1 were 7.23 ?106and
6.04 ? 106cfu/g, respectively. Probiotic yogurts contained 1.85 ? 106cfu/g of L.
acidophilus La5 and 1.79 ? 106cfu/g of B. lactis Bb12 on day 7. Both probiotic
bacteria showed a steady survival rate during a 7-d storage time. The fat content
was 2.5% and was comparable in both yogurt types. The probiotic and conven-
tional yogurt containers were identical and the yogurts had a similar taste and
appearance. The yogurts were specially prepared for this study by Iran Dairy
Industries Co. (Tehran, Iran).
and the results were expressed as mean ? standard deviation. The normality of
the distribution of variables was tested by the Kolmogorov-Smirnov test. For the
duration of diabetes, monounsaturated fatty acid, vitamin A, E, and C intakes,
fasting blood glucose, and insulin that did not follow normal distributions, anal-
samples t tests and chi-square tests. The use of diabetes medication in the two
groups was compared using the Mann-Whitney U test. Differences between the
two groups after the intervention were determined by analysis of covariance,
adjusting for baseline measurements and covariates. In this study, duration of
diabetes and polyunsaturated fatty acid intake were used as possible covariates.
The changes in anthropometric measurements, nutrient intakes, fasting blood
glucose, HbA1c, insulin, and oxidative stress markers of the patients between the
beginning and the end of the trial were compared by paired-samples t test .
Results with P < 0.05 were considered statistically significant.
In this study, four patients were excluded from the statistical
analysis because they needed to change their medication during
the trial or they did not consume the yogurt according to the
plan. Thus, data for 60 patients (23 male and 37 female) were
analyzed (n ¼ 30 for each group). The patients demonstrated
good compliance with the yogurt consumption and no adverse
effects or symptoms were reported. The baseline characteristics
of the patients in the two groups are listed in Table 1. The
H. S. Ejtahed et al. / Nutrition 28 (2012) 539–543
duration of diabetes was significantly different between the
probiotic and conventional groups (P ¼ 0.039). However, other
baseline characteristicsof the patients (age, sex, weight, BMI, and
medications) did not differ between the two groups (P > 0.05).
There were no statistically significant differences in weight and
BMI values between or within groups at the end of the study.
The intake of polyunsaturated fatty acid was significantly
different between the probiotic and conventional groups at the
beginning of the study (P ¼ 0.033). No significant differences in
energy and other nutrient intakes were observed between the
two groups at baseline (P > 0.05). During the study, intakes of
protein, zinc, calcium, and phosphorus significantly increased in
both groups (P < 0.01). No significant changes from baseline
were observed in the other nutrient intakes. At the end of the
study, there were no statistically significant differences between
the two groups for dietary intakes (P > 0.05; Table 2).
There were no statistically significant differences in blood
glucose, HbA1c, and insulin concentration between the two
groups at the beginning of the study (P > 0.05). Fasting blood
glucose and HbA1c were significantly decreased in the probiotic
group compared with the control group (P ¼ 0.009 and P ¼ 0.019,
between groups at the end of the trial (P ¼ 0.955; Table 3). The
intervention group showed 8.68% decrease in fasting blood
glucose concentration from the baseline value (P ¼ 0.001).
Although the differences were not statistically significant, HbA1c
and insulin also decreased in the intervention group during the
study (P ¼ 0.230 and P ¼ 0.654, respectively). In contrast, HbA1c
increased significantly from the baseline in the control group
(P ¼ 0.003; Table 3).
Erythrocyte SOD activity was significantly different between
the probiotic and conventional groups at baseline (P ¼ 0.004).
There were no statistically significant differences between the
two groups in the other variables at baseline (Table 3). Results of
the analysis of covariance showed that there were statistically
significant differences between the two groups in erythrocyte
SOD and GPx activities and TAS at the end of the study when
adjusted for duration of diabetes, polyunsaturated fatty acid
intake, and baseline values (P ¼ 0.007, P ¼ 0.002, and P ¼ 0.014,
respectively). No significant differences were detected in the CAT
activity and MDA concentration between the two groups at the
end of the trial (P > 0.05; Table 3).
As presented in Table 3, erythrocyte SOD and GPx activities
and TAS were significantly increased compared with the base-
line values in the intervention group (P < 0.001, P < 0.001, and
P ¼ 0.001, respectively). No significant changes from baseline
were observed in erythrocyte CAT activity for either group
(P > 0.05; Table 3). The results of paired-samples t test showed
that MDA concentration decreases were significant for the
control and intervention groups (P ¼ 0.005 and P ¼ 0.013,
respectively; Table 3).
In T2DM, free radicals are generated excessively. These free
radicals cause lipid peroxidation and MDA generation .
Moreover, activities of SOD, GPx, and CAT, which scavenge reac-
tive oxygen species, decrease in patients with T2DM . It is
activity, to remove reactive oxygen species. The improvement in
oxidative stress status can contribute to diabetes management
.The present studyshowed thatprobiotic yogurt consumption
significantly decreased fasting blood glucose and HbA1c and
Baseline characteristics of study participants
(n ¼ 30)
51.00 ? 7.32
75.42 ? 11.28
29.14 ? 4.30
4.08 ? 4.28
2 ? 1.25
1 ? 1
(n ¼ 30)
50.87 ? 7.68
76.18 ? 10.94
28.95 ? 3.65
5.82 ? 4.95x
2 ? 1.25
2 ? 2
Duration of diabetes (y)*
BMI, body mass index
* Mean ? SD.
zMedian and interquartile range.
xSignificant difference between groups at baseline (P < 0.05, independent-
samples t test).
Dietary intakes of subjects throughout the study
(n ¼ 30)
(n ¼ 30)
Total fat (g)
Saturated fat (g)
Monounsaturated fat (g)
Polyunsaturated fat (g)
Dietary fiber (g)
Vitamin A (mg)
Vitamin E (mg)
Vitamin C (mg)
1774.99 ? 482.92
1809.67 ? 434.30
1775.20 ? 449.51
1776.67 ? 392.28
232.69 ? 76.15
241.86 ? 68.08
242.88 ? 70.44
239.64 ? 59.54
70.08 ? 20.22
80.82 ? 21.34y
68.12 ? 20.00
77.84 ? 17.99y
68.01 ? 18.27
65.93 ? 16.53
65.49 ? 19.23
61.10 ? 18.63
20.62 ? 7.56
19.21 ? 5.45
20.86 ? 7.19
18.78 ? 5.96
22.76 ? 7.07
21.73 ? 6.28
23.61 ? 10.24
21.88 ? 9.52
18.13 ? 6.42
16.06 ? 5.77
15.03 ? 4.33*
15.01 ? 5.19
14.19 ? 4.44
14.86 ? 6.28
16.05 ? 6.18
15.47 ? 5.54
871.08 ? 663.23
898.22 ? 710.39
1152.05 ? 814.67
1111.54 ? 811.93
12.72 ? 8.38
11.45 ? 7.94
10.27 ? 5.50
10.32 ? 6.12
138.41 ? 61.67
126.96 ? 69.17
152.87 ? 64.93
144.50 ? 54.52
1.59 ? 0.53
1.59 ? 0.55
1.67 ? 0.59
1.57 ? 0.43
9.99 ? 2.64
12.23 ? 3.40y
10.13 ? 3.35
11.43 ? 3.09y
824.86 ? 275.70
1215.11 ? 213.56y
869.76 ? 229.19
1264.69 ? 227.63y
1185.39 ? 319.75
1477.26 ? 324.93y
1173.57 ? 357.33
1462.60 ? 337.15y
Data are presented as mean ? SD
* Significant difference between groups at baseline (P < 0.05, independent-
samples t test).
ySignificant difference within group throughout the study (P < 0.01, paired-
samples t test).
H. S. Ejtahed et al. / Nutrition 28 (2012) 539–543
increased erythrocyte SOD and GPx activities and TAS compared
with conventional yogurt consumption. Furthermore, the MDA
concentration significantly decreased in both groups. However,
insulin concentration and erythrocyte CAT activity remained
unchanged in the intervention group.
In the present study, there were no statistically significant
changes in weight, BMI, and energy within either group during
the study. However, intakes of protein, zinc, calcium, and phos-
phorus significantly increased in both groups throughout the
study. These increases most probably were caused by the yogurt
consumption. There were no statistically significant differences
between the two groups at the end of the study for these
nutrients. Therefore, the observed results in the probiotic group
could not have been caused by the changes inweight and dietary
Chin  reported that T2DM could arise from imbalances of
microflora in the gastrointestinal tract. Larsen et al.  docu-
mented that the intestinal microbiota of patients with T2DM was
relativelyenriched with gram-negative bacteria, belonging tothe
phyla Bacteroidetes and Proteobacteria. The proportion of Fir-
micutes to Bacteroidetes was significantly decreased in the
patients with T2DM compared with the non-diabetic patients
. Therefore, we conducted the first randomized controlled
trial investigating the effects of probiotic yogurton blood glucose
and antioxidant status in patients with T2DM. The findings
support previously reported observational data on the antioxi-
dant property of probiotic yogurt containing L. acidophilus and B.
lactis in young healthy women . Naruszewicz et al. 
investigated the antioxidative effects of L. plantarum in smokers
and found that an L. plantarum intake for 6 wk decreased plasma
F2-isoprostanes concentrations. In a study by Songisepp et al.
, a significant improvement of TAS was seen with the daily
consumption of fermented goat milk containing L. fermentum
ME-3 in healthy persons after 3 wk. Kullisaar et al.  also
reported that goat milk fermented by L. fermentum ME-3
increased total antioxidative activity and decreased lipid perox-
idation markers in healthy persons.
Previous evidence regarding the antidiabetic properties of
probiotics has been limited to animal studies. Harisa et al. 
showed that treatment with L. acidophilus alone or in combina-
tion with acarbose significantly decreased fasting blood sugar,
HbA1c, and MDA concentration in diabetic rats. In an animal
study, Yadav et al.  reported that probiotic dahi, a fermented
milk product containing L. acidophilus and L. casei, had an anti-
oxidative effect on the liver and pancreas tissues of high-
fructose–induced diabetic rats and delayed the onset of glucose
intolerance, hyperglycemia, and hyperinsulinemia. In another
study, Yadav et al.  found that probiotic dahi suppressed
streptozotocin-induced oxidative damage in the pancreatic
tissues of diabetic rats by inhibiting the lipid peroxidation and
preserving the activity of SOD, GPx, and CAT. These effects of
probiotic dahi may slow the decrease of insulin and increase of
blood glucose . Al-Salami et al.  reported that probiotic
treatment had no effect on blood glucose concentration in
healthy rats, but decreased blood glucose in diabetic rats because
of an increased gliclazide (sulfonylurea) bioavailability. In
another study, Matsuzaki et al.  showed that L. casei inhibited
the production of proinflammatory cytokines and decreased
plasma glucose concentration in non–insulin-dependent dia-
The present study, indeed, has reported perhaps the first
evidence of improved glucose metabolism in diabetic patients
and the results are in accordance with the findings of the animal
studies described. However, no statistically significant changes
were observed in HbA1c, insulin concentration, and erythrocyte
CAT activity in the probiotic yogurt group during the study,
which may be explained by the short duration of the study.
The precisemechanisms involved in the antidiabetic effects of
probiotics remain largely unknown. These effects may be partly
related to a probiotics-mediated decrease in oxidative stress.
Moreover, the immune-modulatory and anti-inflammatory
effects of probiotics and the modification of intestinal micro-
flora could be other probable underlying mechanisms. The
inhibition of ascorbate autoxidation, metal ion chelation, and
reduction activity and scavenging of superoxide anion radicals,
hydrogen peroxide, and free radicals are likely to underline the
antioxidative effect of probiotic yogurt [14,36,37]. The relatively
small but significant decrease in lipid peroxidation indicated by
the decreased plasma MDA was not associated with changes in
antioxidant status markers for the control group. The MDA
concentration decrease in bothyogurt groups could be due tothe
antioxidative effect of bioactive peptides released during yogurt
fermentation by proteolytic lactic acid bacteria [38,39].
Fermented milks have been reported as dietary sources of
natural antioxidants because of the presence of antioxidant
peptides. Most identified bioactive peptides were derived from
as-casein and have been shown to exhibit free radical scavenging
and inhibit enzymatic and non-enzymatic lipid peroxidation
. The antioxidant peptides derived from whey protein are
likely the result of the presence of cysteine-rich proteins that aid
in the synthesis of glutathione, a potent intracellular antioxidant
. Although the yogurt for both trial groups can exert anti-
oxidative effects by bioactive peptides, the results showed that
Effects of 6 wk of probiotic and conventional yogurt consumption on blood
glucose, hemoglobin A1c, insulin, and oxidative stress markers
(n ¼ 30)
(n ¼ 30)
SOD (U/g Hb)
GPx (U/g Hb)
CAT (K/g Hb)
7.35 ? 1.28
7.53 ? 1.32
8.06 ? 2.49
7.36 ? 2.41y,z
6.87 ? 0.81
7.17 ? 0.66z
7.29 ? 1.21
7.17 ? 1.24y
6.31 ? 3.72
6.50 ? 3.57
7.47 ? 4.89
6.97 ? 4.49
1161.59 ? 246.01
1136.54 ? 256.26
975.80 ? 238.34*
1113.69 ? 177.77y,z
30.28 ? 4.40
30.12 ? 4.23
29.03 ? 4.29
29.81 ? 4.58yz
141.40 ? 25.78
151.15 ? 36.98
148.81 ? 34.56
146.57 ? 34.05
0.93 ? 0.20
0.92 ? 0.16
0.90 ? 0.18
0.96 ? 0.18y,z
2.81 ? 0.65
2.55 ? 0.60z
2.79 ? 0.62
2.53 ? 0.65z
CAT, catalase; GPx, glutathione peroxidase; Hb, hemoglobin; MDA, malondial-
dehyde; SOD, superoxide dismutase; TAS, total antioxidant status
Data are presented as mean ? SD
* Significant difference between groups at baseline (P < 0.01, independent-
samples t test).
ySignificant difference between groups after intervention (P < 0.05, analysis of
covariance, adjusted for duration of diabetes, polyunsaturated fatty acid intake,
and baseline values).
zSignificant difference within group throughout the study (P < 0.01, paired-
samples t test).
H. S. Ejtahed et al. / Nutrition 28 (2012) 539–543
probiotic yogurt was more effective in increasing antioxidative
activity than conventional yogurt.
The limitations of this study included its short duration and
the absence of a control group that consumed no yogurt. More-
over, many exclusion criteria in this study could limit the
generalizability of the results. Therefore, further investigations
with longer duration and a no-yogurt control group, and a larger
trial with some form of stratification are needed to confirm the
positive effect of probiotic yogurt on the management of dia-
betes. Further studies on the effects of probiotics on intestinal
microflora composition and intestinal transit time in diabetic
patients would be useful.
This trial showed that consuming 300 g/d of probiotic yogurt
containing L. acidophilus La5 and B. lactis Bb12 improved the
antioxidant status and fasting blood glucose in patients
with T2DM. These findings suggest that probiotic yogurt is
a functional food that can exert antidiabetic and antioxidant
The authors thank the Iran Dairy Industries Company for
supplying the probiotic and conventional yogurts and support-
ing this study.
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