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e-SPEN Journal xxx (2012) 1e6

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Original article

Effects of a whole rice diet on metabolic parameters and inammatory markers


in prediabetes
Bin Wang a, Raj Medapalli a, Jin Xu a, Weijing Cai b, Xue Chen b, John C. He a, Jaime Uribarri a, *
a
b

Department of Medicine The Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA
Department of Geriatrics, The Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA

a r t i c l e i n f o

s u m m a r y

Article history:
Received 7 August 2012
Accepted 12 November 2012

Background and aims: Epidemiological studies have shown an association between consumption of white
rice and prevalence of insulin resistance. We wanted to test the effect of substituting brown rice for white
rice on insulin resistance.
Methods: A group of Chinese American (n 100) with screening pre-diabetes in the area of Flushing,
New York City, were randomized to either continue their usual white rice intake (n 51) or change to
brown rice (n 49) for 3 months. Fasting blood was obtained at baseline and end of study in both groups
for measurement of circulating and cellular (peripheral mononuclear cells) metabolic and inammatory
markers.
Results: Only 58 subjects (white rice 28 and brown rice 30) nished the study. Their analysis shows
signicant weight loss and fall of systolic and diastolic blood pressure only in those ingesting brown rice.
Insulin and HOMA, serum AGEs and 8-isoprostane decreased, while SIRT1 mRNA increased in the brown
rice group as compared to the white rice group.
Conclusions: Substituting brown rice for white rice in a pre-diabetes population with high daily
consumption of rice has a very benecial effect in improving their metabolic risk factors. Further studies
are needed to conrm these ndings.
2012 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights
reserved.

Keywords:
Oxidative stress
Insulin resistance
Metabolic syndrome
Dietary ber
AGEs

Recently, the China National Diabetes and Metabolic Disorders


Study Group reported that prevalence of diabetes and pre-diabetes
in the Chinese population was 9.7% and 15.5%, respectively.1 They
also found that the prevalence of diabetes was higher among urban
residents than among rural residents (11.4% vs. 8.2%) suggesting
that environmental factors, such as consuming more rened grain
foods, play a key role in the pathogenesis of diabetes. Pre-diabetes
is also a major public health issue in Chinese American population.
Among Chinese immigrants in New York City, the age-adjusted
prevalence of pre-diabetes was 34.6% in a population even with
normal BMI.2
Food products derived from cereal grains constitute a major part
of the daily diet of Chinese population as well as Chinese Americans. For example, typically a Chinese American eats rice about 9.5
times a week on an average.3 However, most of these foods are
derived from rened grain. During the rening process grains are
stripped of their bran and germ, which depletes several biologically
* Corresponding author. One Gustave Levy Place, Box 1147, New York, NY 10029,
USA. Tel.: 1 212 241 1887; fax: 1 212 369 9330.
E-mail address: jaime.uribarri@mssm.edu (J. Uribarri).

active constituents including ber, anti-oxidants, phytoestrogens


and minerals. From observational studies there is evidence for
a protective effect of whole-grain foods with regard to the development of type 2 diabetes.4e8 More recently, higher intake of whole
grains was also associated with decreases in insulin resistance e
a risk factor related to the development of type 2 diabetes.9e12
However, the randomized clinical studies in this eld are very
limited.12e14
Thus, we wanted to study the benecial effect of higher whole
grain intake on insulin sensitivity in a group of Chinese American
patients with pre-diabetes in this randomized prospective study. In
addition, we went a step further by exploring the potential mechanisms by which this benet may occur. Our hypothesis is that
a diet that is rich in whole grain foods rather than rened grain
foods improves insulin sensitivity and reduces levels of inammatory markers in patients who have pre-diabetes. Therefore, we
assessed the effect of consuming a brown rice-rich diet on levels of
advanced glycation end products (AGEs) and other markers of
inammation and oxidative stress e all of which have been shown
to play an important role in the pathogenesis of diabetes mellitus.15e17

2212-8263/$36.00 2012 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.clnme.2012.11.001

Please cite this article in press as: Wang B, et al., Effects of a whole rice diet on metabolic parameters and inammatory markers in prediabetes,
e-SPEN Journal (2012), http://dx.doi.org/10.1016/j.clnme.2012.11.001

B. Wang et al. / e-SPEN Journal xxx (2012) 1e6

1. Subjects and methods


Any adult subject with pre-diabetes (dened as hemoglobin A1c
levels between 5.7 and 6.4% identied within 6 months of initiation
of study) receiving their medical care at an outpatient clinic in
Flushing, New York City was asked to participate in the study if they
did not have any exclusion criteria. Exclusion criteria included the
following: a) diagnosis of diabetes mellitus, renal disease or
cardiovascular disease (apart from hypertension), b) body weight
uctuation of more than 10% in the past 6 months, c) planning to
change signicantly level of physical activity during the time of
study, d) planning to move out of town or take a vacation for 14
days during the time of the study, e) current smoker, g)
consumption of greater than 2 alcoholic drinks per day, h) allergy to
any type of grain, i) special diets, j) use of medications that would
affect blood glucose levels (e.g. steroids) and g) any current
malignancy.
All participants consented to participate in the study and signed
informed consent. The study protocol and the informed consent
were approved by the Mount Sinai School of Medicine Institutional
Review Board. The study was registered as a clinical trial in
clinicaltrials.gov with the identier NCT01248286.
After signing informed consent, subjects were randomized to
either continue their regular intake of white rice or change to
brown rice (see below) for the next 12 weeks.
1.1. Treatment arms
For each subject, total energy requirement was estimated to
maintain body weight. Every month all subjects were provided
free both types of rice. The supplies provided were enough to
meet the calculated total energy requirements for a 4-week
period. No rice was provided for the family or other household members. Subjects were encouraged to prepare rice items
in their daily meals with the food items provided for the
duration of the study and they were also advised not to change
their usual patterns of cooking and eating. When the subjects
attended the clinic to collect the food supplies, they were asked
to ll out a food compliance questionnaire, which included
questions about their food intake during the previous day. This
questionnaire elicited information about the number of meals
that each participant had on that day and if the rice was part of
that meal. If the participant had a meal, which included rice
items during a meal, the questionnaire also elicited if the
participant used the supplied food material to prepare that meal
as well as an estimate of what percentage of that meal derived
from rice items.
At baseline subjects also had an assessment of their physical
activity categorical score using the short form of the International Physical Activity Questionnaire (http://www.ipaq.ki.se/
ipaq.htm).
The white and brown rice were obtained from Grace Health
Products, Inc (Flushing, NY) and Nomura & Company, Inc (Burlingame, California), respectively. The nutrient composition of both
rice were measured at Certied Laboratories, Inc. (Plaineld, NY)
according to standardized analytical method and is shown in
Table 1. As expected, brown rice had higher content of ber and of
some nutrients, minerals (especially potassium and magnesium)
and vitamins (especially vitamin E and folic acid) than white rice.
The content of AGEs (carboxymethyl-lysine and methylglyoxalderivatives) in cooked rice (boiled in water for 30 min) was not
signicantly different between both groups.
At the initial and nal visit (12 weeks) patients received a full
medical evaluation, had anthropometric parameters measured and
had fasting blood drawn for laboratory tests.

Table 1
Nutrient composition of white rice and brown rice.
Nutrienta

White rice

Brown rice

Calories (kcal)
Protein (g)
Fat (g)
Ash (g)
Total carbohydrates (g)
Sugars (g)
Fiber (g)
Cholesterol (g)
Saturated fat (% of fat)
Monounsaturated fat (% of fat)
Polyunsaturated fat (% of fat)
Trans fat (% of fat)

352
6.72
1.18
0.42
78.54
0
5.7
0
43
27
30
0

362
7.86
3.11
1.42
75.58
0
15.4
0
30
39
31
0

Mineralsa
Sodium (mg)
Iron (mg)
Potassium (mg)
Magnesium (mg)
Calcium (mg)
Zinc (mg)
Copper (mg)

0
0.1
120
34
5
0.72
1.8

0
0.71
270
110
9
1.4
2.8

0
0
1.1
0.48
0.07
1.2
4.8

0
0
11.8
0.27
0.12
2.1
42.4

Vitaminsa
Vitamin A (I.U.)
Vitamin C (I.U.)
Vitamin E (I.U.)
Thiamine (mg)
Riboavin (mg)
Niacin (mg)
Folic acid (mcg)
AGEsb
CML (kilounits)
MG (nmol)
a
b

10
520

9
440

Each nutrient, mineral or vitamin is expressed as units/100 g rice.


Measured in cooked rice (see Methods).

2. Methods
2.1. Dietary intake
Daily dietary AGE content from 3-day food records that
emphasized cooking methods was estimated from a database of
w560 foods which listed AGE values18 expressed as AGE Equivalents (Eq/day) (1 AGE equivalent 1000 kilounits).18 Nutrient
calculations were estimated from the same food records using an
online software program (http://ndb.nal.usda.gov/ndb/foods/lis).
2.2. Measurement of AGEs and insulin and inammation markers
N-carboxymethyl-lysine (CML) and methylglyoxal (MG) derivatives in serum and in food were quantied by ELISAs, using two
not cross-reactive monoclonal antibodies (4G9 and MG3D11 mabs)
raised against synthetic standards, CML-BSA and MG-BSA, respectively.19 Insulin was measured by an ELISA kit (ALPCO Diagnostics,
Salem, NH). Insulin resistance was estimated according to the
Homeostasis Model Assessment (HOMA) index as: FI  Fasting
glucose/22.5, where FI is insulin in mU/mL and fasting glucose is
expressed in mmol/L. Leptin and adiponectin were determined
with human leptin or adiponectin ELISA kits (Millipore, Billerica,
MA). Isoprostane was measured by an ELISA kit (Cayman, Ann
Arbor, Michigan). TNFa protein was measured in MNC lysates by an
ELISA kit (Biosource International, Camarillo, CA).
2.3. In vitro grain AGE binding study
To determine whether rice had a direct effect binding AGEs in
the gastrointestinal tract we performed AGE binding studies. AGE-

Please cite this article in press as: Wang B, et al., Effects of a whole rice diet on metabolic parameters and inammatory markers in prediabetes,
e-SPEN Journal (2012), http://dx.doi.org/10.1016/j.clnme.2012.11.001

B. Wang et al. / e-SPEN Journal xxx (2012) 1e6

BSA (100 mg/ml) was dissolved in PBS with pH at 1.0 or 7.0.


Homogenized cooked rice (white or brown) was added into the
different pH PBS-AGE solutions to a 10% (wt/vol) concentration. The
AGE-grain solution was subsequently shaken at room temperature
for 24 h. After centrifugation, the supernatant was sampled for AGE
ELISA assay (see above).
2.4. Peripheral blood mononuclear cells (MNCs)
MNCs were separated from fasting, EDTA anti-coagulated blood
by FicolleHypaque Plus gradient (American Biosciences, Uppsala,
Sweden) and used to isolate mRNA and protein.19 Total RNA was
extracted by Trizol (Molecular Probes, Inc). The extracted RNA had
an A260/280 ratio between 1.8 and 2.0. Total RNA was reversetranscribed using Superscript III RT (Invitrogen).
2.5. Quantitative RT-PCR assay
SIRT1 mRNA expression was analyzed by quantitative SYBR
Green real-time PCR. Amplication was performed with 40 cycles
of denaturation at 95  C for 15 s, annealing at 55  C for 20 s and
elongation at 72  C for 30 s. Primer sequences were: forward
primer 50 -CGGAAACAATACCTCCACCT-30 , reverse primer 50 -CACCCCAGCTCCAGTTAGAA. During thermal cycling, emission from each
sample was recorded and the raw uorescence data was processed
using SDS software to produce threshold cycle (Ct) values for each
sample. b-actin and GAPDH housekeeping genes were used for
internal normalization. The transcript copy number of target genes
was determined based on their Ct values.20
2.6. Statistical analysis
The KolmogoroveSmirnov goodness-of-t test was used to test
for normal distribution. Variables not normally distributed were
logarithmically converted for analyses. Differences of means
between groups were analyzed by Students t test or ANOVA, followed by the Bonferroni correction for multiple comparisons,
depending on the number of groups. Correlation analyses were also
examined by the Pearson correlation coefcient.
There were only two visits for blood tests: baseline and at the
end of three months. Signicance of changes during the interventional study was assessed by comparing percentage of change from
baseline to the end of the study between both groups by unpaired
student t test. This could only be done in those subjects who came
for their nal visit. Signicant differences were dened as a value of
P < 0.05 and are based on two-sided tests.
Linear regression analysis was used to examine the potential
effect of weight loss on other changes associated with the brown
rice intervention. First, we determined the association between
study group and each one of the other biochemical/metabolic
parameters (sCML, sMG, insulin and 8-isoprostane); then we added
weight change to the model and determined whether the signicance of the association remained or disappeared. Data analysis
was performed using SPSS 17.0 software (SPSS, Chicago, IL).
3. Results
3.1. Baseline
All participants were ethnically Chinese attending a medical
practice located in the neighborhood of Flushing in New York City.
We screened a large database of patients attending the clinic (about
500), from which 100 patients were selected based on the exclusion/inclusion criteria detailed in methods and randomly assigned
to either brown rice (n 49) or white rice (n 51) groups. The two

groups were very similar with respect to most baseline characteristics, except for subjects on the brown rice group who had a higher
BMI (Table 2) and less physical activity categorical score (70% score
1, 14% score 2 and 15% score 3 vs 33% score 1, 19% score 2 and 48%
score 3 in subjects in the white rice group). In the white rice group
only 2 men and 1 woman (10%) had 2 or more components of the
metabolic syndrome; 4 men and 12 women (55%) had high waist
circumference, 3 men and 1 woman (14%) had high blood pressure,
3 men and 4 women (24%) had high triglycerides, 6 men and 2
women (28%) had low HDL cholesterol and 2 men and 3 women
(17%) had high fasting blood glucose. These percents were not
signicantly different from those in the brown rice group in which
2 men 1 woman (10%) had 2 or more components of the metabolic
syndrome, 5 men and 15 women (71%) had high waist circumference, 0 man and 1 woman (3%) had high blood pressure, 6 men and
6 women (43%) had high triglycerides, 6 men and 2 women (29%)
had low HDL cholesterol and (29%), and 3 men and 3 women (21%)
had high fasting blood glucose. There were no differences between
both groups in baseline daily dietary intakes of nutrients or AGEs.
At baseline, HOMA correlated mostly with BMI (r 0.308,
p 0.020), but there were signicant associations among several
other inammatory markers (Table 3)
3.2. Interventional study
Only 58 subjects completed the study (brown rice 30 and
white rice 28). Twelve subjects were discontinued from the study
because they were found to be smoking (one from each group),
eating mixed rice (2 in the brown rice group and 5 in the white rice
group) or had an HgbA1c higher than 6.6% at baseline (two from the
white rice group). The remainder 30 subjects did not show up for

Table 2
Baseline characteristics of the study participants.

Variable

White rice
(n 29)

Brown rice
(n 28)

Female, n (%)
Age (years)
Weight (kg)
Waist circumference (cm)
BMI (kg/m2)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Daily caloric intake (kcal/day)
Daily protein intake (g/day)
Daily CHOa intake (g/day)
Daily fat intake (g/day)
Daily AGE intake (AGE Eq/day)
Glucose (mg/dl)
HbA1c (%)
Total cholesterol (mg/dl)
HDL cholesterol (mg/dl)
LDL cholesterol (mg/dl)
Triglycerides (mg/dl)
Serum creatinine (mg/dl)
Insulin (mU/ml)
HOMA-IR
Leptin (ng/ml)
Adiponectin (mg/ml)
Serum CMLb (U/ml)
Serum MGb (nmol/ml)
TNFa (pg/mg protein)
8-Isoprostane (pg/ml)

20 (69)
50  9
63  10
84  8
25.0  2.2
118  12
75  8
1374  286
51  22
175  57
42  11
4.5  1.4
91  8
5.84  0.23
189  30
56  16
104  21
150  112
0.75  0.13
5.1  4.4
1.15  0.98
8.7  9
8.8  4
6.5  1.7
0.86  0.18
62  28
105  32

18 (64)
55  9
65  8
87  6
26.5  3.0
123  10
75  6
1537  362
61  24
175  83
68  39
5.6  1.4
91  8
5.95  0.20
185  32
51  14
101  28
168  114
0.76  0.16
6.3  4.9
1.42  1.27
7.2  4
6.9  4
6.6  1.8
0.89  0.16
71  36
102  32

0.852
0.065
0.507
0.069
0.034
0.133
0.822
0.303
0.368
0.998
0.103
0.086
0.977
0.103
0.677
0.260
0.585
0.537
0.792
0.342
0.314
0.430
0.103
0.822
0.641
0.312
0.783

All values expressed as mean  SD.


P value indicates the statistical difference between means of both groups at baseline
(unpaired Students t test).
a
CHO carbohydrates.
b
Serum CML serum 3N-carboxymethyl-lysine; serum MG serum methylglyoxal derivatives.

Please cite this article in press as: Wang B, et al., Effects of a whole rice diet on metabolic parameters and inammatory markers in prediabetes,
e-SPEN Journal (2012), http://dx.doi.org/10.1016/j.clnme.2012.11.001

B. Wang et al. / e-SPEN Journal xxx (2012) 1e6

Table 3
Univariate correlations between several markers of inammation and oxidative stress at baseline.
BMI (kg/m2) Waist (cm) Insulin (mU/ml) HOMA (index) Leptin (ng/ml) Adipoa (mg/ml) sCML (U/ml) sMG (nmol/ml) TNFa (pg/mg) Isoa (pg/ml)
2

BMI (kg/m )
Waist (cm)

.720
.001
Insulin mU/ml
.272
.041
HOMA (index) .308
.020
Leptin (ng/ml) .087
.522
Adipoa (mg/ml) .199
.139
sCML (U/ml)
.370
.005
sMG (nmol/ml) .309
.019
TNFa (pg/mg)
.252
.059
Isoa (pg/ml)
.323
.014

.720
.001
1
.109
.419
.162
.230
.210
.117
.186
.165
.336
.011
341
.009
.200
.135
.158
.241

.272
.041
.109
.419
1
.989
.000
.117
.126
.219
.101
.101
455
.040
.765
.214
.109
.028
.836

.308
.020
.162
.230
.989
.000
1
.129
.338
.241
.071
.050
.710
.050
.710
.257
.053
.025
.854

.087
.522
.210
.117
.126
.349
.129
.338
1
.433
.001
279
.036
.279
.036
.249
.062
.004
.978

.199
.139
.186
.165
.219
.101
.241
.071
.433
.001
1
.220
.100
.234
.080
.307
.020
.042
.759

.370
.005
.336 .011
.101
.455
.086
.525
.014
.915
.220
.100
1
.757
.000
.440
.001
.740
.000

.309
.019
.341
.009
.040
.765
.050
.710
.279
.036
.234
.080
.757
.000
1
.304
.021
.498
.001

.252
.059
.200
.135
.214
.109
.257
.053
.249
.062
.307
.020
.440
.001
.304
.021
1

.323
.014
.158
.241
.028
.836
.025
.854
.004
.978
.042
.759
.740
.000
.498
.001
.407
.002
1

.407
.002

Pearsons correlation coefcients calculated by SPSS (see Methods).


a
Adipo adiponectin; Iso 8-isoprostanes.

their nal visit for different reasons including travel out of state or
to China or medical reasons (same number in both groups), but
there were 8 subjects who withdrew from the brown rice group
because they did not like its taste. All 58 subjects who completed
the study were very compliant with the foods based on the questionnaires and our monitoring phone calls during the interventional period. We are presenting the data on these 58 patients who
completed the study. None of the medications were changed
during the study period in these patients. We have asked patients
to provide food records and estimated their daily caloric, nutrients,
and AGE intake during the intervention. We found that the daily
dietary intake of calories, nutrients and AGEs did not change
signicantly during the intervention in both groups.
3.3. Anthropometric parameters and blood pressure
Body weight, waist circumference, BMI and both systolic and
diastolic blood pressures decreased signicantly only in the brown
rice group (Table 4).

protein declined signicantly from baseline in both groups without


any signicant between groups difference (Table 4).
PMNC SIRT1 mRNA increased signicantly only in the brown
rice group (SIRT ratio end to beginning of study 2  0.46 in the
whole grain versus 1.0  0.09 in the rened grain; p 0.029).
Linear regression models demonstrated that changes in serum
AGEs (CML and MG) and insulin remained signicant after adjusted
for weight changes. Changes in 8-isoprostane lost signicance after
adjusting for weight changes.
3.6. AGE binding by rice
To determine whether reduction of blood AGE levels is due to
the binding of AGEs by the brown rice, we incubated AGE BSA with
homogenates from each kind of rice (cooked) for 24 h in vitro and
found that either rice bound minimally to AGEs (less than 1% AGE
binding to rice).
Table 4
Effect of substituting brown rice for white rice on several parameters.
Brown rice (n 28)

3.4. Glycemic control, insulin resistance, leptin, adiponectin and


blood lipids
Neither intervention affected signicantly fasting blood glucose
or HbA1c, but levels of plasma insulin decreased signicantly in the
brown rice group. The percent of changes (decrease) in the HOMA
was signicantly more in brown rice group than white rice group,
indicating that brown rice improves insulin sensitivity (Table 4)
Adiponectin had a tendency to increase in the brown rice group
and to decrease in the white rice group, but did not reach statistical
signicance (Table 4). Leptin was essentially unchanged in both
groups (Table 4).
Levels of lipids did not change signicantly with the intervention, but levels of LDL cholesterol and triglycerides show a distinct
fall in the brown rice group (Table 4).
3.5. Circulating AGEs and other markers of oxidative stress and
inammation
Brown rice diet was associated with a signicant decrease of
sCML and sMG as well as 8-isoprostane. Interestingly, PMNC TNFa

Weight (kg)
Waist (cm)
BMI (kg/m2)
SysBP (mmHg)
DiasBP (mmHg)
Leptin (ng/ml)
Adipoa (mg/ml)
HbA1c (%)
FBGa(mg/dl)
Insulin (mU/ml)
HOMA (index)
HDL (mg/dl)
LDL (mg/dl)
Trigla(mg/dl)
sCML (U/ml)
sMG (nmol/ml)
TNFa(pg/mg)
8-Isoa(pg/ml)

Baseline
64.9  8
87  6
26.5  3
123  10
75  6
7.2  4
6.9  4
5.9  0.2
91  8
6.3  5
1.5  1.2
51  14
101  28
168  114
6.6  2
0.89  0.16
71  36
102  32

End
63.4
82
25.8
114
72
7.5
7.2
5.9
93
5.5
1.3
52
98
145
5.4
0.73
55
87




















White rice (n 29)


8
6
3
13
6
6
4
0.2
9
5
1.2
12
24
119
1
0.20
24
24

Baseline
63.3  10
84  8
24.9  2
118  12
75  8
8.7  9
8.8  4
5.8  0.2
91  8
5.1  4
1.1  1.0
55  16
104  20
150  111
6.5  2
0.86  0.18
62  28
105  32

End
63.8
84
25.0
118
76
9.1
8.5
5.8
89
5.2
1.1
54
108
150
6.7
0.90
51
105




















10
8
3
18
8
9
4
0.2
7
4
0.8
14
29
77
1
0.24
19
29

P
0.001
0.001
0.001
0.001
0.004
0.079
0.074
0.687
0.069
0.001
0.005
0.197
0.880
0.153
0.026
0.015
0.991
0.050

All values are expressed as mean  SD; FBG fasting blood glucose;
Trigl triglycerides; 8-iso 8-isoprostanes.
P indicates difference of percent changes between baseline and end of the study
between both groups (unpaired Students t test).
a
Adipo adiponectin.

Please cite this article in press as: Wang B, et al., Effects of a whole rice diet on metabolic parameters and inammatory markers in prediabetes,
e-SPEN Journal (2012), http://dx.doi.org/10.1016/j.clnme.2012.11.001

B. Wang et al. / e-SPEN Journal xxx (2012) 1e6

4. Discussion
The current study shows that the short-term substitution of
white rice with brown rice in the daily diet of Chinese subjects with
pre-diabetes living in New York City was associated with
a substantial improvement in metabolic risk factors. Weight, BMI
and waist circumference as well as circulating levels of insulin,
HOMA, sAGEs (both CML and MG) and 8-isoprostane decreased,
while PMNC SIRT1 mRNA levels increased signicantly with
this diet.
This is the rst prospective randomized clinical study to determine the effects of brown rice diet in a Chinese American population. This is also the rst study to determine the effects of brown
rice diet in subjects with well-dened pre-diabetes. In addition,
this study determined whether replacing the white rice with brown
rice attenuated the inammation markers and serum AGE levels,
two critical risk factors for diabetic complications. The nding that
replacing white rice with brown rice increased SIRT1 expression
also indicates a potential novel mechanism by which brown rice
provides benecial effects. However, the detailed mechanisms
required further studies.
One argument could be made that loss of weight and other
metabolic effects followed overall less intake of food and therefore
decreased caloric intake in subjects on the brown rice. It is
conceivable that the different color, taste and texture of brown rice
compared to white rice, the one usually consumed by all these
subjects at baseline, might have had a deterrent effect and some
participants might have changed their eating habits and consumed
less rice and therefore less calories. However, the participants were
frequently interviewed and questioned about dietary intake during
the study and they show signicant adherence to their isocaloric
diet. Providing rice for free to the participants might have markedly
enhanced their compliance and we believe caloric intake was
similar between the two groups. Moreover, our study is consistent
with previous reports showing that a whole grain-rich diet is
associated with reduction of body weight and blood pressure21 and
reduced markers of inammation.13,22,23
The main difference between both types of rice lies in the processing procedure to produce white rice, during which most of the
bran and germ are removed. We must emphasize, however, in the
current study we used different sources of white and brown rice
and therefore the differences between both grains go beyond the
processing to produce white rice. Nutrient analyses showed that
brown rice was higher in bers, many nutrients, vitamins, minerals
and vitamins. It would be difcult to determine whether the effect
observed in the current study results from just one of these
components; e.g. higher ber, or simply reect the balanced
inuence of many of them. It is conceivably that levels of folic acid
might have played some role since the folate content of brown rice
has been shown to decrease by more than 50% after cooking
(boiling in water for 30 min) as a result of a combination of thermal
degradation and leaching of the vitamin into the cooking water.24
The effect of brown rice decreasing serum AGEs is an interesting
one and its mechanisms cannot be fully elucidated in the current
study. Clearly, the difference in AGE content between white and
brown rice is not enough to explain this change. The total dietary
AGE intake both at baseline and throughout the study was not
different between both groups of subjects. Brown rice by
decreasing oxidative stress might have a secondary effect
decreasing AGEs.25 Recently it has been shown that a low AGE diet,
unrelated to rice intake, reproduces most of the ndings observed
in the current study, namely decrease circulating levels of AGEs and
markers of oxidative stress, while increasing SIRT1 levels.20
Therefore it was tempting to speculate that the increased ber
content of the brown rice might have had a direct effect interfering

with the gastrointestinal absorption of AGEs26 as the primary event.


However, the lack of AGE binding in vitro by rice homogenates at
least eliminates a direct effect on AGE trapping.26
Other potential mechanism for the improved metabolic risk
factor associated with brown rice could be the effect of increased
dietary ber on the gut microora.27 However, this requires further
validation.
Although epidemiologic studies have shown whole grain intake
is inversely associated with risk of type 2 diabetes28 it is unclear
whether substituting brown rice for white rice can improve
metabolic risk factors in a prospective study. In fact, recently, Zhang
et al.14 were unable to demonstrate any benets of the substitution.
Their different results compared to our study may reect differences in study design. First, their population had higher percent of
overt diabetes among those on white rice, while we excluded
patients with diabetes. Secondly, their white rice was prepared by
rening the actual brown rice used, while in our study we used
completely different brands of white and brown rice. Finally, the
nutrient composition as well as the amount of ber in their brown
rice was also very different from ours.
We acknowledge that our denition of insulin resistance using
the surrogate index HOMA-IR, instead of other more recognized
methods of evaluation of insulin sensitivity such as oral glucose
tolerance test or clamps, is a limitation of our study. Nevertheless,
HOMA-IR is the least invasive and expensive measure of insulin
resistance and represents the most widely insulin resistance index
utilized in daily clinical practice. Moreover, this is only a pilot study
and further studies with more sophisticated assessment of insulin
sensitivity would have to be performed in the future to conrm our
ndings.
Other limitations of the current study are the relatively small
number of subjects, the high dropout rate from study and the short
duration of the intervention. Furthermore, we cannot be absolutely
certain about the compliance of participants in the consumption of
the assigned rice portions.
In summary, we have demonstrated in a pilot study that
substituting brown rice for white rice in a population with high
daily consumption of rice has a benecial effect in improving their
metabolic risk factors.
Funding sources
None.
Statement of authorship
B.W. and R.M. performed the clinical study; J.X., W.C. and X.C.
performed all clinical laboratory measurements; J.H. and J.U.
designed and supervised the study and wrote the nal manuscript.
All authors reviewed and edited the nal manuscript.
Conict of interest statement
None of the authors declare any conicts of interest.
Acknowledgements
The authors thank Dr. Helen Vlassara for the measurement of
AGEs in her research laboratory at the Mount Sinai School of
Medicine, New York, NY.
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Please cite this article in press as: Wang B, et al., Effects of a whole rice diet on metabolic parameters and inammatory markers in prediabetes,
e-SPEN Journal (2012), http://dx.doi.org/10.1016/j.clnme.2012.11.001