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Rooholahzadeganetal.
Nutrition & Metabolism (2023) 20:11
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RESEARCH
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Open Access
Nutrition & Metabolism
The eect ofDASH diet onglycemic
response, meta-inammation andserum LPS
inobese patients withNAFLD: adouble-blind
controlled randomized clinical trial
Farnaz Rooholahzadegan1, Sara Arefhosseini1, Helda Tutunchi2, Taghi Badali1, Manuchehr Khoshbaten3 and
Mehrangiz Ebrahimi‑Mameghani4*
Abstract
Background As dietary approaches to stop hypertension (DASH) dietary pattern has been shown to be effective
in hypertension and obesity, the present study investigated the effects of following DASH diet on glycemic, meta‑
inflammation, lipopolysaccharides (LPS) and liver function in obese patients with non‑alcoholic fatty liver disease
(NAFLD).
Methods In this double‑blind controlled randomized clinical trial, 40 obese patients with NAFLD were randomly allo‑
cated into either “DASH diet” (n = 20) or calorie‑restricted diet as "Control” (n = 20) group for 8 weeks. Anthropometric
measures, blood pressure, glycemic response, liver enzymes, toll‑like reseptor‑4 (TLR‑4) and monocyte chemoattract‑
ant protein (MCP‑1) and LPS as well as Dixon’s DASH diet index were assessed at baseline and after 8 weeks.
Results After 8 weeks, although all obesity indices decreased significantly in both groups, the reduction in all anthro‑
pometric measures were significantly greater in DASH vs control group, after adjusting for baseline values and weight
change. Fasting glucose level decreased in both group, however, no inter‑group significant difference was found at
the end of study. Nevertheless, serum levels of hemoglobin A1c (HbA1c), TLR‑4, MCP‑1 and LPS as well as aspartate
aminotransferase (AST) decreased significantly in DASH group, after adjusting for baseline values and weight change
(p < 0.001, p = 0.004, p = 0.027, p = 0.011, and p = 0.008, respectively). The estimated number needed to treats (NNTs)
for one and two grade reductions in NAFLD severity following DASH diet were 2.5 and 6.67, respectively.
Conclusion Adherence to DASH diet could significantly improve weight, glycemia, inflammation and liver function
in obese patients with NAFLD.
Keywords Dietary approaches to stop hypertension, Glycemic control, Inflammation, Lipoploysaccharides, Non‑
alcoholic fatty liver disease
*Correspondence:
Mehrangiz Ebrahimi‑Mameghani
ebrahimimamagani@tbzmed.ac.ir
1 Student Research Committee, Tabriz University of Medical Sciences,
Tabriz, Iran
2 Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz,
Iran
3 Department of Internal Medicine, Faculty of Medicine, Tabriz University
of Medical Sciences, Tabriz, Iran
4 Nutrition Research Center, Department of Biochemistry and Diet
Therapy, Faculty of Nutrition and Food Sciences, Tabriz University
of Medical Sciences, Tabriz, Iran
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Page 2 of 14
Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
Introduction
Exposure to an “obesogenic” environment such as sus-
tained positive energy balance due to increased food
supply and the overconsumption of energy-dense low
nutrient-dense foods as well as modern sedentary life-
style leads to excessive intrahepatic fat accumulation and
increased adiposity known as nonalcoholic fatty liver
disease (NAFLD), as a public health issue [1–3]. NAFLD
is considered as an umbrella term that includes differ-
ent types of fatty liver diseases unrelated to alcohol con-
sumption [4]. Due to the metabolic roots of NAFLD, it
has been recently proposed that to rename NAFLD as
metabolic dysfunction-associated fatty liver disease or
’MAFLD’ [5]. A recent systematic review and meta-anal-
ysis through the extraction of available epidemiological
data on fatty liver disease demonstrated that MAFLD
has an astonishingly high prevalence rate in overweight
and obese adults [6]. Moreover, the global prevalence of
NAFLD among general population is projected to raise
up to 33.5%, which is largely related to obesity epidemic
[7]. Genetic and epigenetic factors such as insulin resist-
ance (IR), inflammation, oxidative stress and changes
in gut microbiota are involved in the pathophysiology
of NAFLD known as "Multi-Hit" [8]. IR-disturbances in
intra-cellular insulin signaling pathways- plays a funda-
mental role in NAFLD [9]. Furthermore, simple steatosis
could be followed by a number of metabolic abnormali-
ties such as decreased fatty acid oxidation in the liver,
increased de novo lipogenesis and adipose tissue lypoli-
sis resulted in IR and in turn, IR is associated with other
endocrine and metabolic disorders [9, 10]. e inter-
relationship between obesity and NAFLD has been fre-
quently reported and indicating the role of adipose tissue
in regulating endocrine signaling pathways such as hor-
mones, adipokines and pro-inflammatory cytokine [11,
12]. NAFLD is also called as the hepatic manifestation of
metabolic syndrome (Mets) because of the coexistence
of visceral obesity, IR, dyslipidemia, and hypertension [8,
13]. In addition, hypertrophy/ hyperplasia of adipose tis-
sue is considered as one of the contributing factor in a
low-grade chronic inflammation and metabolic dysfunc-
tion known as “meta‐inflammation” [14]. It is caused by
an increased macrophage accumulation and the release
of adipokines, cytokines and chemokines e.g. tumor
necrosis factor α (TNF-α), toll-like receptors-4 (TLR-4),
monocyte chemoattractant protein (MCP‐1) and some
interleukins (inc. IL‐6, IL‐8, IL‐1β) [14]. ere is evidence
that weight reduction can be effective in the secretion
of inflammatory markers [14]. TLR-4 plays a vital role
in recognizing lipopolysaccharides (LPS)- an indicator
of pathogenic bacteria invasion- and mediates signaling
to produce pro-inflammatory cytokines [14]. Moreover,
excessive adipose tissues releases free fatty acids (FFAs)
due to degradation of triglycerides [15]. LPS and FFAs
bind to TLR4 of monocytes/macrophages and produce
inflammatory mediators, and therefore, lead to the pro-
longed production of inflammatory cytokines [15].
Despite the lack of an approved therapeutic approach
in the treatment of NAFLD, evidence-based guidelines
establish the fundamental role of lifestyle modifica-
tions, particularly calorie restriction, healthy diet, and
regular physical activity in improving hepatic steatosis
and histological features of NAFLD [16, 17]. In clinical
and preclinical studies, several natural compounds have
shown favorable effects in the prevention, inhibition
and treatment of metabolic disorders [18–23]. is evi-
dence represents a promising strategy for NALFD, whose
pathogenesis is multifactorial [24]. Patients with NAFLD
mostly consume diet which is low in whole grains, cere-
als, fruits, and vegetables and high in red meat, refined-
grains and sugars, typically named as Western dietary
pattern [25–27]. Moreover, results of a meta-analysis
revealed the role of red meat intake and soft drinks in
increased likelihood of NAFLD [28, 29]. One of the die-
tary strategies that has been studied in NAFLD manage-
ment is the Dietary Approaches to Stop Hypertension
(DASH) dietary pattern approved in the prevention and
treatment of hypertension [30]. Previous studies have also
shown that DASH diet has beneficial effects on several
other disorders including obesity, Mets, type 2 diabetes
mellitus (T2DM), cardiovascular disease, and depres-
sion [31–33]. DASH diet underlines fruits, vegetables,
low-fat dairy products, whole grains, poultry, fish, nuts,
seeds, and legumes intakes accompanied by reduction in
fats, red meat, sweets, and sugar-containing drinks [30].
Meanwhile, this diet is low in sodium (< 2400mg/day)
and saturated fat while rich in protein, fiber, calcium,
magnesium, potassium, zinc, and folate [34, 35]. Watz-
inger etal. [36] in a cross-sectional study showed that
the DASH score was correlated to lower liver fat content
and NAFLD. Indeed, in a case–control study, an inverse
association was found between adherence to a DASH-
style diet and odds of NAFLD [37]. Similarly, Maskarinec
etal. [38] in the Multiethnic Cohort Study showed that
higher quality diets during mid-to-late adulthood were
associated with a lower risk of NAFLD. Moreover, results
of a recent nested case–control study in the Multiethnic
Cohort revealed that higher DASH score was negatively
correlated with NAFLD risk [39]. e only interventional
study aimed to assess 8-week adherence to DASH diet
compared with low calorie diet showed improvements in
body weight, liver enzymes, IR, lipid profile, inflamma-
tory and oxidative stress biomarkers [40]. As a system-
atic review and meta-analysis of randomized controlled
clinical trials reported that DASH diet seems to be more
suitable dietary approach for weight loss compared
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Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
with low-energy diets and lack of interventional study
in investigating the effect of DASH diet on NAFLD [41,
42], this study compared the effect of adherence to DASH
diet compared with calorie-restricted diet (CRD) on gly-
cemic response, meta-inflammation and serum LPS in
obese patients with NAFLD.
Materials andmethods
Study design
is double-blinded controlled randomized clinical trial
was designed to examine the adherence to DASH diet
compared with CRD on cardiometabolic, inflammatory
biomarkers and LPS in obese patients with NAFLD. e
study was conducted according to the Declaration of Hel-
sinki and approved by the ethics committee of research
vice-chancellor and also registered in the Iranian Registry
of Clinical Trials (IRCT20100209003320N17). In addi-
tion, an informed consent form was read and signed by
the patients at baseline.
Participants
Sixty two males and females newly diagnosed patients
with mild and moderate NAFLD aged 20–50years with
body mass index (BMI) = 30–40 kg/m2 were enrolled.
NAFLD was confirmed by a single radiologist using
ultrasonography (Sonoace X4 Medisio, South Korea) in a
fasting state and then, liver steatosis severity was catego-
rized into three grades, i.e. grade I as "mild", grade II as
"moderate" based on Hamaguchi etal. [43].
e exclusion criteria were as follow: alcohol con-
sumption, pregnancy, breastfeeding, menopause, regular
exercise, following weight loss diet 3months before the
study, taking medications such as anti-diabetic, anti-
lipidemic, anti-hypertensive, antibiotics, corticosteroids,
oral contraceptives and anti-inflammatory drugs, as well
as suffering from liver, kidney, thyroid, gastro-intestinal,
autoimmune diseases, T2DM, polycystic ovary syndrome
(PCOS), and cancer.
Sample size
According to mean and standard deviation of serum
MCP-1 reported by Wamberg etal. [44] and by consider-
ing 95% confidence interval (CI) and %80 power among
patients with NAFLD using sample size software (PASS;
NCSS, LLC, US), sample size was found 20 for each
group which then increased to 24 by considering 10%
drop-out rate.
Randomization, blinding, andintervention
To randomly allocate the patients into two groups, Ran-
dom Allocation Software (RAS) and randomized block
procedure were used. e patients were assigned into
either DASH or CRD groups (1:1) by an assistant not
involved in the trial. Size 3 randomized block procedure
was applied as follows; gender (female vs male), age (18–
35 yrs. vs 36–55 yrs.) and BMI (< 35 kg/m2 vs ≥ 35 kg/
m2)]. Before randomization for treatment, the assign-
ment was concealed.
Energy requirement was estimated individually accord-
ing to Mifflin formula and weight loss diet was planned
by reducing 500 kcal from the estimated energy for
all the patients [45]. Macronutrient distribution was
55–60%, < 30%, and 10–15% of energy from carbohy-
drates, fat, and protein, respectively. Meal plans were
prepared based on these calculations and the food-
based dietary guidelines for Iranians (available at http://
www. fao. org/ nutri tion/ educa tion/ food- based dieta
ry- guide lines/ regio ns/ count ries/ iran/ fr/) for CRD. For
DASH diet, weight loss diet was designed according
to DASH dietary pattern [46]. e DASH diet was rich
in fruits, vegetables, whole grains, and low-fat dairy
products and low in saturated fats, cholesterol, refined
grains, and sweets. Suggested sodium in the DASH diet
was < 2400mg/day.
Food group exchange list and food album were deliv-
ered to each patient to follow the prescribed diet. e
participants were also given a full explanation on how to
use food exchange lists to replace the foods they did not
have access to, by the foods of equal calorie from the cor-
responding food groups as well as delivering food group
exchange list and food album to follow the prescribed
diet.
Assessment ofanthropometric measures, dietary intake,
andphysical activity
At the beginning and end of the trial, personal and dis-
ease details, anthropometric measurements, physical
activity levels and dietary intakes were assessed. Weight
and height were measured using Seca stadiometer (Ham-
burg, Germany) to the nearest 100g and 0.5cm with low
clothes without shoes, respectively. BMI was estimated as
weight (Kg) divided by height squared (m2). e circum-
ferences of waist and hip were also measured at the half-
way between the lower ribs and the iliac crest and around
the widest portion of the buttocks to the nearest 0.1cm,
respectively. en, BMI, Waist-to-hip ratio (WHR) and
waist-to-height ratio (WHtR) were estimated.
A 3-day food record was completed by the patients at
baseline, week 4 and 8 and then, mean of each 3-day food
record was calculated for each food item, converted to
grams and ml, finally energy and macronutrient intakes
were obtained using Nutrition IV software (First Data-
bank: Hearst, San Bruno, CA, USA) at baseline and after
8weeks.
Furthermore, Dixon’s DASH diet index was estimated
to confirm adherence to DASH diet [46]. Foods were
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Page 4 of 14
Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
categorized into 9 components based on the following
daily recommendations: total fruits (≥ 4 servings), total
vegetables (≥ 4 servings), whole grains ((≥ 4 servings),
low-fat dairy products (≥ 2 servings), legumes, seeds
and nuts (≥ 4 servings), meat/meat equivalents (< 170g),
added sugar (< 3% of total daily energy), alcoholic bev-
erages (≤ 2 drink) and saturated fat (< 5% of total daily).
Foods were categorized into 9 components based on the
following daily recommendations were scored 1 point
and other than recommendation were scored zero point:
total fruits (≥ 4 servings), total vegetables (≥ 4 s ervings),
whole grains ((≥ 4 servings), low-fat dairy products (≥ 2
servings), legumes, seeds and nuts (≥ 4 servings), meat/
meat equivalents (< 170 g), added sugar (< 3% of total
daily energy), alcoholic beverages (≤ 2 drink) and satu-
rated fat (< 5% of total daily). An overall adherence to
DASH diet, therefore, was obtained by summing up the
points ranging from 0 to 9 [47–49].
To assess physical activity level, the international physi-
cal activity questionnaire-short form (IPAQ-SF) was
applied through face-to-face interview [50]. e patients
were asked to report the time spent doing each of the
defined intensity-varied activities during the past week to
calculate metabolic equivalent of task (MET-hours/week)
score. en, the participants were categorized into: “low”,
“moderate”, or “high” activity level [50].
Laboratory assays
At baseline and at the end of study, after 12–14h over-
night fasting, blood sample was obtained from each
patient and serum was separated. Metabolic factors
including serum glucose, alanine aminotransferase (ALT)
and aspartate transaminase (AST) concentrations were
determined at the same day while the rest was stored
at − 70 °C until assays. Serum alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) concentra-
tions were assessed at baseline and at the end of study
using the International Federation of Clinical Chemistry
(IFCC) approved method. Hemoglobin A1C (HbA1c)
was assessed using photometry in whole blood using Pars
Azmoun Company kit (Pars Azmoun, Iran) and Hitachi
auto analyzer (Hitachi-917, Tokyo, Japan). Furthermore,
serum levels of TLR-4, MCP-1, and LPS were assessed
using enzyme-linked immunosorbent assay (ELISA) kit
(LSBio, Seattle, WA). According to complete blood count
(CBC) results, white blood cell (WBC)-derived inflam-
matory indices including neutrophil to lymphocyte ratio
(NLR), monocyte to lymphocyte ratio (MLR), platelets
to to lymphocyte ratio (PLR), monocyte to high-den-
sity lipoproteincholesterol (HDL-C) ratio (mHDL) and
finally, systemic inflammation response index (SIRI)- as
an index reflecting the host immune and inflammation
balance—was estimated: SIRI = Neutrophil × monocy te/
lymphocyte [51–53].
Study outcomes
Changes in energy and macronutrient intakes, serum gly-
cemic indices, MCP-1 and TLR-4, LPS, blood pressure,
and anthropometric indices were considered as the pri-
mary outcomes whereas changes in serum levels of liver
enzymes and NAFLD grade were considered as the sec-
ondary outcomes.
Statistical analysis
All statistical analyses were performed using SPSS Statis-
tics software (IBM SPSS Statistics, Armonk, USA, latest
version). e distribution of continuous variables was
checked using Kolmogorov–Smirnov test. For assess-
ing both primary and secondary outcomes, after treat-
ment approach was applied. Data were expressed as
mean ± standard deviation (SD), median (min, max),
and number (%) for continuous variables with symmetric
and asymmetric distribution and categorical variables,
respectively. Inter-group differences in the continuous
and categorical variables at baseline were performed
using independent samples t- and Chi-square tests,
respectively. Paired samples t- and Sign tests were used
for changes variables. At the end of the trial, the analy-
sis of covariance (ANCOVA) test was used to compare
between group changes in variables by adjusting for the
confounders (i.e., baseline values and weight change).
Absolute risk reduction (ARR) was calculated based on
the difference in the event rate between DASH and con-
trol groups and then number needed to treat (NNT) was
estimated according to the following formula: NNT = 1/
ARR. e significance level was defined at p value lower
than 0.05.
Results
Of totally 62 patients enrolled the trial, 40 subjects (20
patients in each group) completed the trial while 11
patients in each group lost to follow because of not fol-
lowing the prescribed diet (Fig.1).
Table 1 demonstrates baseline characteristics in two
studied groups. More than half of the studied patients
in both groups were women and married. At baseline,
no significant differences were found for not only demo-
graphic characteristics but also for NAFDL severity and
physical activity level between the groups.
Changes in dietary energy and nutrient intakes over
the study in control and DASH group are presented
in Table 2. Apart from monounsaturated fatty acids
(MUFA), dietary fiber, sodium and magnesium at base-
line, no significant differences were found in not only
energy and nutrient intakes but also the proportion of
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Page 5 of 14
Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
macronutrients from energy between the groups before
and after the study. At baseline and end of the study,
saturated fat intake in DASH group was significantly
less than in control group (p < 0.001). Moreover, no sig-
nificant changes were observed in physical activity level
in both groups over the intervention (data not shown).
erefore, physical activity and dietary energy and
nutrient intakes were not considered as confounders in
data analysis.
Table3 demonstrates changes in anthropometric meas-
ures, obesity indices, as well as metabolic and inflam-
matory biomarkers in studied groups. Apart from hip
circumference (HC), the reduction in all anthropomet-
ric measures were significantly greater in DASH group
Fig. 1 Flow chart of the study
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Page 6 of 14
Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
than in control group, after adjusting for baseline val-
ues and weight change. Although fasting blood sugar
(FBS) decreased in both groups, between-group com-
parison did not reveal any significant difference after
8weeks, after adjusting for baseline values and weight
change. Nevertheless, despite significant difference in
serum HbA1c between the groups at baseline, a signifi-
cant reduction in HbA1c was observed in DASH group
(P < 0.001) while there was an increase in serum HbA1c
in control group. Inter-group changes in serum HbA1c
was statistically significant, after adjusting for baseline
values and weight change (p < 0.001) (Table3).
ere were significant reductions in serum levels
of TLR-4, MCP-1 and LPS in DASH group while no
changes were found in these variables in control group
(Table3). After adjusting for baseline values and weight
change, inter-group analysis showed significant differ-
ences in serum concentrations of TLR-4, MCP-1 and
LPS. Among WBC-derived inflammatory indices, only
PLR change was statistically significant between the two
groups, after adjusting for the baseline values and weight
change (p = 0.019).
Regarding serum liver enzymes, significant reduc-
tions in both serum levels of AST and ALT were found in
DASH group whereas serum ALT decreased significantly
in control group (Table3). After adjusting for baseline
values and weight change, there was only significant
between-group difference in serum concentration of AST
(p = 0.008).
Table 4 summarizes the effectiveness of DASH diet
in NAFLD improvement. It was observed significant
improvement in liver steatosis for both group, i.e. the
greatest improvement as being free from NAFLD was
seen for DASH group (80%) and control group (40%),
respectively. e estimated NNTs due to 8-week follow-
ing DASH diet compared with control group for one and
two grade improvements in NAFLD severity were 2.5 and
6.67, respectively.
Discussion
e results of the present study designed to examine the
effect of adherence to DASH diet compared with CRD on
glycemic response, meta-inflammation and serum LPS in
obese patients with NAFLD showed greater reductions in
weight and obesity indices, serum levels of HbA1c, AST,
LPS and inflammatory biomarkers.
As energy for both DASH diet and CRD had been esti-
mated based on Mifflin formula (around 1550–1650kcal/
day) with similar macronutrient distribution from energy,
no significant differences in energy and macronutrient
Table 1 Baseline characteristic of the study participants
DASH, Dietary Approaches to Stop Hypertension, BMI Body mass index, NAFLD Non-alcoholic fatty liver disease. Data are presented as mean ± SD for numerical data
and number (%) for categorical variables
*p value for Independent sample t-test
**p value for Chi square test
Variable DASH
(N = 20) Control (N = 20) p
Age (yr.) 38.80 ± 9.98 37.10 ± 9.74 0.589*
Weight (Kg) 93.32 ± 19.51 93.49 ± 13.98 0.976*
Height (cm) 166.49 ± 12.0 165.52 ± 7.86 0.764*
BMI (Kg/m2) 33.43 ± 4.09 34.02 ± 3.61 0.632*
N (%) N (%)
Female 13 (65.0) 12 (60.0) 0.594**
Married 17 (85.0) 15 (75.0) 0. 683**
Educational level
Less than Diploma 6 (30.0) 3 (15.0) 0.520**
Diploma 6 (30.0) 9 (45.0)
University degrees 8 (40.0) 8 (40.0)
Physical activity level
Light 10 (50.0) 11 (55.0) 0.674**
Moderate 7 (35.0) 8 (40.0)
Heavy 3 (15.0) 1 (5.0)
NAFLD severity
Mild 10 (50.0) 12 (60.0) 0.751**
Moderate 10 (50.0) 8 (40.0)
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Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
intakes were found between the groups (Table2). Results
of the estimation of Dixon’s DASH diet index revealed
good adherence to DASH diet i.e. score 8 to 9 (ranged
0–9) at baseline and end of the study, respectively. ere-
fore, changes in the study outcomes could be attributed
to the weight loss intervention diet. Apart from saturated
fat intake in DASH group which was approximately half
of that in CRD group (p < 0.001) at baseline and end of
the study, there were no significant differences in micro-
nutrients intakes (being the characteristic of DASH diet
i.e. sodium, potassium, magnesium, calcium and vitamin
D) between the groups at the end of the study.
Our findings also revealed that reductions in weight
and obesity indices were significantly greater in DASH
group than CRD group, after adjusting for the confound-
ers (Table3). ere is evidence indicating that as DASH
diet includes high fruits, vegetables, dietary fiber and cal-
cium as well as low fat intake, particularly in the form of
dairy products, and also simple sugar, following DASH
diet is an effective approach in weight loss in obesity
and a number of metabolic diseases [31–33]. For exam-
ple, Asemi et al. [54] showed that adherence to DASH
diet compared with usual low-calorie diet in patients
with PCOS for 8 weeks resulted in greater reductions
in weight and BMI. Similar findings were also reported
Table 2 Daily dietary intakes before and after the study
Variable DASH
(N = 20) Control
(N = 20) P
Energy (Kcal)
Baseline 1585.60 ± 187.67 1629.50 ± 206.54 0.488**
End 1553.00 ± 134.07 1640.10 ± 174.38 0.104***
P* 0.326 0.895
Carbohydrates (g)
Baseline 227.55 ± 31.46 234.40 ± 36.20 0.527**
End
P*219.59 ± 22.94
0.243 232.80 ± 25.70
0.949 0.123***
Protein (g)
Baseline 73.09 ± 8.17 75.72 ± 12.51 0.436**
End 69.52 ± 8.94 70.85 ± 13.68 0.978***
P* 0.192 0.164
Fat (g)
Baseline 46.17 ± 6.18 46.78 ± 10.11 0.841**
End 48.21 ± 5.61 49.84 ± 7.41 0.461***
P* 0.094 0.270
Carbohydrates (%)
Baseline 57.33 ± 2.28 57.07 ± 3.46 0.780**
End 56.54 ± 2.89 56.66 ± 3.60 0.910***
P*0.290 0.692
Protein (%)
Baseline 18.47 ± 1.00 18.99 ± 2.26 0.354**
End 17.90 ± 1.66 17.46 ± 2.70 0.535***
P*0.211 0.054
Fat (%)
Baseline 26.23 ± 2.03 25.96 ± 4.00 0.791**
End 27.94 ± 2.23 27.49 ± 3.13 0.609***
P*0.006 0.109
SFA (g)
Baseline 9.37 ± 2.73 18.41 ± 5.66 < 0.001**
End 9.69 ± 2.00 17.39 ± 3.28 < 0.001***
P*0.242 0.309
MUFA(g)
Baseline 21.09 ± 3.22 14.25 ± 3.99 < 0.001**
End 21.63 ± 3.45 15.60 ± 3.48 0.057***
P*0.415 0.222
PUFA (g)
Baseline 8.89 ± 1.18 7.63 ± 4.45 0.227**
End 10.03 ± 1.93 9.82 ± 4.81 0.868***
P*0.088 0.096
Dietary fiber (g)
Baseline 23.06 ± 6.45 17.89 ± 5.57 0.010**
End 21.93 ± 6.32 17.19 ± 6.32 0.794***
P*0.065 0.346
Sodium (mg)
Baseline 925.69 ± 344.87 1341.12 ± 504.75 0.004**
End 987.39 ± 345.33 1277.44 ± 412.15 0.078***
P* 0.465 0.536
Table 2 (continued)
Variable DASH
(N = 20) Control
(N = 20) P
Magnesium (mg)
Baseline 277.76 ± 65.74 227.29 ± 69.42 0.023**
End 266.94 ± 70.42 211.73 ± 70.25 0.705***
P* 0.340 0.249
Potassium (mg)
Baseline 3181.75 ± 1457.01 2916.95 ± 834.20
End 3510.35 ± 1016.14 2715.85 ± 970.19 0.485**
P* 0.106 0.296 0.530***
Calcium (mg)
Baseline 856.98 ± 308.63 700.03 ± 269.69 0.095**
End 921.32 ± 291.93 592.40 ± 228.59 0.074***
P* 0.357 0.062
Vitamin D (µg)
Baseline 2.14 ± 1.21 1.81 ± 1.34 0.426**
End 2.25 ± 0.84 1.08 ± 1.11 0.091***
P*0.850 0.048
Bold indicates p<0.05 is statistically signicant
DASH Dietary Approaches to Stop Hypertension, SFA Saturated fatty acid, MUFA
Monounsaturated fatty acid, PUFA Polyunsaturated fatty acid. Mean (SD) and
Mean Dierence (95% CI) are presented for data
*p value for paired- t test
**p value for Independent samples t-test
***p value for ANCOVA test (adjusted for baseline values and weight change)
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Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
Table 3 Anthropometric measures, metabolic and inflammatory biomarkers before and after the study
Variable DASH Control P
(N = 20) (N = 20)
Weight (Kg)
Baseline 93.32 ± 19.51 93.49 ± 13.98 0.976**
End 85.57 ± 18.62 87.88 ± 13.88 0.021***
MD (95% CI), P*−7.75 (−9.34, −6.17), > 0.001 − 5.61 (− 6.71, − 4.50). < 0.001
BMI (Kg/m2)
Baseline 33.43 ± 4.09 34.02 ± 3.61 0.632**
End 30.64 ± 4.06 31.96 ± 3.57 0.025***
MD (95% CI), P*−2.79 (−3.35, −2.22), < 0.001 −2.06 (−2.47, −1.64), < 0.001
WC (cm)
Baseline 111.25 ± 12.29 109.92 ± 9.80 0.708**
End 103.32 ± 12.67 105.0 ± 9.60 0.002***
MD (95% CI), P*−7.92 (−9.58, −6.27), < 0.001 −4.92 (−5.94, −3.91), < 0.001
HC (cm) 115.42 ± 10.47 115.92 ± 5.84
Baseline 111.07 ± 11.44 112.20 ± 5.99 0.853**
End −4.35 (−5.22, −3.48), < 0.001 −3.72 (−4.63, −2.82), < 0.001 0.323***
MD (95% CI), P*
WHR 0.95 ± 0.07
Baseline 0.96 ± 0.04 0.93 ± 0.07 0.406**
End 0.93 ± 0.05 −0.01 (−0.02, 0.00), 0.031 0.014***
MD (95% CI), P*−0.03 (−0.05, −0.02), < 0.001
WHtR
Baseline 0.67 ± 0.06 0.66 ± 0.05 0.821**
End 0.62 ± 0.06 0.63 ± 0.05 0.002***
MD (95% CI), P*−0.05 (−0.06, −0.04), < 0.001 −0.03 (−0.04, −0.02), < 0.001
FBS (mg/dl)
Baseline 93.41 ± 9.63 93.12 ± 9.63 0.933**
End 90.76 ± 5.69 90.64 ± 4.69 0.923***
MD (95% CI), P*−2.64 (−5.82, 0.53), 0.098 −0.21 (−0.37, −0.05), 0.013
HbA1c (%)
Baseline 5.30 ± 0.35 5.49 ± 0.49 < 0.001**
End 5.09 ± 0.34 5.56 ± 0.32 < 0.001***
MD (95% CI), P*−2.49 (−7.54, 2.57), 0.314 0.07 (−0.08, 0.21), 0.340
TLR-4 (ng/ml)
Baseline 0.82 ± 0.11 0.80 ± 0.17 0.656**
End 0.70 ± 0.13 0.82 ± 0.14 0.004***
MD (95% CI), P*−0.13 (−0.20, −0.05),0.003 0.02 (−0.05, 0.08), 0.634
MCP-1 (pg/ml)
Baseline 110.75 ± 7.56 11.64 ± 16.48 0.828**
End 100.44 ± 10.69 110.01 ± 11.79 0.027***
MD (95% CI), P*−10.32 (−16.36, −4.27), 0.002 −1.64 (−8.12, 4.85), 0.603
NLR
Baseline 1.92 ± 0.81 1.81 ± 0.64 0.238**
End 1.94 ± 0.83 1.71 ± 0.60 0.176***
MD (95% CI), P*26.51 (19.08, 33.94), < 0.001 37.44 (29.64, 45.23), < 0.001
MLR
Baseline 0.17 ± 0.09 0.16 ± 0.07 0.732**
End 0.23 ± 0.34 0.16 ± 0.08 0.179***
MD (95% CI), P*0.06 (−0.09, 0.21), 0.399 0.004 (−0.16, 0.02), 0.701
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Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
by subsequent studies conducted on patients with
NAFLD [40, 55]. Meanwhile, Rifai etal. [56] in patients
with heart failure failed to show any noticeable effect on
weight and BMI after 3months. In a randomized con-
trolled trial in 2021, 12-week following DASH diet with
and without exercise on anthropometric indices, DASH
diet plus exercise resulted in significantly lower weight
and WHR, although at the end of the study, the inter-
group differences were not statistically significant [57].
Moreover, a cross-sectional study on 305 overweight and
obese women showed that adherence to DASH diet was
inversely associated with greater weight reduction [58].
Soltani etal. [42] in a meta-analysis of randomized con-
trolled trials on the effect of low calorie DASH diet on
weight (N = 10), BMI (N = 6) and WC (N = 2) demon-
strated its lowering effect on the studied anthropometric
measures. It appears that DASH diet because of its low
energy density, high content of dietary fiber, particularly
due to the higher intake of whole grains and vegetables
could be effective in delaying carbohydrate absorption
and increasing satiety [42].
Although the results of the present trial failed to
show any difference in micronutrients such as calcium
and magnesium between the two diets at the end of the
study, cummulative evidence shows that DASH diet con-
tains high calcium and magnesium. Studies have dem-
onstrated that dietary calcium increases lipolysis and
plays an important role in weight management [34, 59].
Hence, calcium and magnesium intakes are inversely
related with obesity due to their roles in the saponifi-
cantion of fatty acids [34]. On the other hand, increased
sodium intake-which is low in DASH diet-results in fat
Table 3 (continued)
Variable DASH Control P
(N = 20) (N = 20)
PLR
Baseline 0.12 ± 0.03 0.11 ± 0.4 0.731**
End 0.12 ± 0.04 0.12 ± 0.05 0.019***
MD (95% CI), P*−0.002 (−0.010, 0.006), 0.680 0.01 (0.001, 0.02), 0.030
SIRI
Baseline 688.53 ± 437.71 720.85 ± 622.22 0.850**
End 862.13 ± 1139.21 706.92 ± 610.50 0.151***
MD (95% CI), P*173.59 (−308.57, 655.76), 0.460 −13.92 (−68.06, 40.22), 0.597
mHDL
Baseline 7.59 ± 3.67 10.56 ± 8.65 0.166**
End 13.47 ± 29.77 9.44 ± 6.70 0.080***
MD (95% CI), P*5.87 (−7.30, 19.04), 0.362 − 1.12 (− 2.70, 0.45), 0.152
LPS (pg/ml)
Baseline 21.66 ± 1.83 20.72 ± 2.43 0.174**
End 18.91 ± 2.98 20.90 ± 2.36 0.011***
MD (95% CI), P*−2.75 (−4.17, −1.33), < 0.001 0.18 (− 1.18, 1.54), 0.785
AST (IU/L)
Baseline 24.10 ± 10.91 26.75 ± 9.28 0.413**
End 18.40 ± 6.57 25.05 ± 8.70 0.008***
MD (95% CI), P*−5.70 (−9.42, −1.98), 0.005 −1.70 (−3.53, 0.13), 0.067
ALT (IU/L)
Baseline 27.20 ± 14.0 37.35 ± 18.37 0.057**
End 18.75 ± 8.91 31.60 ± 16.24 0.149***
MD (95% CI), P*−8.45 (−12.89, −4.01), 0.001 −5.75 (−10.46, −1.04), 0.019
Bold indicates p<0.05 is statistically signicant
DASH Dietary Approaches to Stop Hypertension, BMI Body mass index, WC Waist circumference, HC Hip circumference, WHR Waist to hip ratio, WHtR Waist to height
ratio, FBS Fasting blood sugar, HbA1c hemoglobin A1c, NLR Neutrophil to lymphocyte, MLR Monocyte to lymphocyte, PLR Platelets to lymphocyte, SIRI Systemic
inammation response index, mHDL Monocyte to high-density lipoproteincholesterol ratio, AST Aspartate aminotransferase, ALT Alanine aminotransferase, TLR-4 Toll-
like receptor-4, MCP-1 Monocyte chemoattractant protein-1, LPS Lipopolysaccharides
Mean (SD) and Mean Dierence (95% CI) are presented for data
*p value for paired- t test;
**p value for Independent samples t-test;
***p value for ANCOVA test (adjusted for baseline values and weight change)
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Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
accumulation through increasing leptin [42]. erefore,
following DASH diet for long term appears to help in
weight control.
Previous studies have also demonstrated that high
sodium intake is associated with the risk of NAFLD [60].
Uetake etal. [61]. found that high-salt diet exacerbated
nonalcoholic steatohepatitis in high-fat diet-fed lipopro-
tein receptor-1 (LOX-1) transgenic /apoE knockout mice
and that this effect was associated with the induction of
oxidative and inflammatory processes. Oxidative stress
and chronic inflammation play a major role in patho-
physiology of NAFLD [62]. A high-salt diet also activates
the aldose reductase-fructokinase pathway in the liver
and hypothalamus, which leads to endogenous fructose
production with the development of leptin resistance and
hyperphagia that cause obesity, IR, and NAFLD [63].
Our results also failed to find any significant difference
in serum FBS change after 8weeks between the groups,
however, a significant reduction in serum HbA1c was
observed in DASH group (P < 0.001) compared with an
increase in control group, after adjusting for the con-
founding factors (p < 0.001) (Table 3). ere is evidence
with a great emphasis on the consumption of whole
grains, fruits and vegetables in DASH diet, therefore, the
high content of dietary fiber in DASH diet decreases car-
bohydrate absorption and lowers blood glucose level [54].
Furthermore, DASH diet also includes food items with
low glycemic index and low energy content which is effi-
cient not only in hypertension but also could be consid-
ered as an efficient dietary approach in the management
of IR-related chronic diseases [54, 64]. Shirani etal. [65]
have reported that the adherence to DASH diet is more
likely to be associated with lower risk of hyperglycemia.
In this study, apart from PLR (p = 0.019), there were
no significant inter-group differences in WBC-derived
inflammatory biomarkers at the end of study. Neverthe-
less, serum levels of TLR-4, MCP-1 and LPS decreased
significantly in DASH group while no changes were found
in control group. Even after adjusting for confounding
variables, between-group analysis showed significant dif-
ferences in serum concentrations of TLR-4, MCP-1 and
LPS (Table3). Fung et al. [66] in a prospective cohort
study showed that DASH diet was associated with lower
serum interleukin-6 (IL-6) and C- reactive protein (CRP).
Holt et al. [67] also illustrated that high consumption
of fruits and vegetables decreased IL-6, CRP and TNF-
α. Similar findings have been reported on patients with
metabolic syndrome [68], T2DM [69], Mets [70] and
NAFLD [40]. DASH diet has shown favorable effects on
serum CRP and hs-CRP levels been through previous
studies [55, 71, 72]. However, Asemi etal. [73] on those
with gestational diabetes (24–24 weeks) reported no
effect of DASH diet on CRP level. Studies investigating
the effect of DASH diet with other inflammatory bio-
markers are few. Taheri etal. [58] showed that DASH diet
compared with other dietary pattern did not affect serum
levels of MCP-1. A systematic review on 16 observational
and 13 interventional studies concluded that plant-based
dietary patterns (such as Mediterranean or DASH diet)
reduce inflammatory biomarkers such as serum hs-CRP,
TNF-α and IL-6 [74].
Because DASH diet is rich in fruits and vegetables as
well as flavonoids with antioxidant activity, adherence
to DASH diet results in a decrease in free radicals, lipid
peroxidation and inflammation and in turn, leads to
reduced secretion of leptin and therefore, weight control
[64]. Hence, considering the close link between oxidative
stress and inflammation, inflammatory cells can produce
large amounts of reactive oxygen species (ROS)- as a
part of mechanism for immunological defense-to protect
human organisms against invading pathogens [8].
Moreover, studies havedemonstrated that thelow gly-
cemic index diet may decrease inflammation by slowing
glucose absorption, altering gut microflora and therefore
suppress the production of inflammatory cytokines, stim-
ulate the production of short-chain fatty acids in intra-
lumen which results in lower circulating FFA levels and
thus subsequent inflammation [42]. Furthermore, parallel
to the effect of DASH diet on meta-inflammation observed
Table 4 Changes in liver steatosis
Bold indicate p<0.05 is statistically signicant
* Chi square test
DASH, Dietary Approaches to Stop Hypertension; Non-alcoholic fatty liver
disease; ARR, Attributable risk reduction; NNT, Number needed to treat
Variable DASH
(N = 20) Control
(N = 20) P*
NAFLD severity
Baseline 0.273
Grade I 10(50.0) 8 (40.0)
Grade II 10 (50.0) 12 (60.0)
End
Grade 0 12 (60.0) 4(20.0) 0.012
Grade I 8 (40.0) 12 (60.0)
Grade II 0 (0.0) 4 (20.0)
Liver steatosis severity
No change 1 (5.0) 12 (60.0)
1 grade reduction 16 (80.0) 8(40.0)
2 grade reduction 3 (15.0) 0 (0.0)
ARR
1 grade reduction (%) 40 –
2 grade reduction (%) 15 –
NNT
1 grade reduction 2.5 –
2 grade reduction 6.67 –
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Page 11 of 14
Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
in serum levels of TLR-4 and MCP-1, the concentration of
LPS decreased. Studies investigating the effect of DASH
diet on serum LPS is limited. Observational and inter-
ventional studies have suggested that phytochemicals and
other compounds present in DASH diet are directly or
indirectly attributed in the modulation of inflammatory
biomarkers as well as intestinal permeability and therefore,
the body’s susceptible to infection [75]. e link between
obesity and high intestinal permeability has been well doc-
umented. e systemic levels of LPS are elevated in obese
individuals through several mechanisms. e.g. impaired
clearance in the liver, alterations in the gut microbiota,
permeability, motility and enzyme levels, and serum levels
of HDL-C [75]. Intercellular tight junctions can regulate
intestinal permeability and factors such as fatty acids and
proinflammatory cytokines are necessary to maintaining
intestinal mucosa integrity [75]. erefore, it appears obe-
sity as well as impaired oxidative stress and chronic inflam-
mation in response to the characteristics of DASH diet are
involved in the improvement of inflammation.
Serum AST and ALT reduced significantly in DASH
group whereas serum ALT decreased significantly in con-
trol group (Table3). After adjusting for the confounders,
there was only significant between-group difference in
serum concentration of AST (p = 0.008) which is in line
with other studies. For example, reduced levels of serum
liver enzymes followed by DASH diet have been reported
in patients with T2DM [69] and NAFLD [40, 76]. Moreo-
ver, Xiao et al. [55] in population-based cohort study
illustrated that following DASH diet was less likely to be
associated with NAFLD risk, particularly in women and
those without abdominal obesity. Mahdavi etal. [71] also
reported following DASH diet led to reductions in liver
steatosis and fibrosis in male adolescents with hemophilia
after 10weeks. In the present study, the NNT was calcu-
lated for assessing the clinical importance of DASH diet.
e estimated NNTs for 8-week following DASH diet com-
pared with RCT for one and two grade improvements in
NAFLD severity were found 2.5 and 6.67, respectively.
Our study had several strengths including studying
NAFLD patients who newly diagnosed without receiv-
ing any medication or treatment, providing an individual-
ized low-calorie diet as an approved strategy for NAFLD
management) on the basis of DASH dietary pattern, good
adherence to DASH diet by the patients and assessing spe-
cific inflammatory biomarkers compared with previous
studies. However, lack of liver biopsy because of ethical
considerations, not assessing other inflammatory factors as
well as insulin resistance indices could be considered as the
study limitations.
Conclusion
It is concluded that following DASH diet for 8 weeks
could significantly improve liver function in patients
with NAFLD due to reduced weight and BMI, glycemic
response, and meta-inflammation.
Abbreviations
ALT Alanine aminotransferase
ANCOVA Analysis of covariance
ARR Absolute risk reduction
AST Aspartate aminotransferase
BMI Body mass index
BP Blood pressure
CBC Complete blood count
CI Confidence interval
CRD Calorie‑restricted diet
CRP C‑ reactive protein
DASH Dietary Approaches to Stop Hypertension
DBP Diastolic blood pressure
ELISA Enzyme‑linked immunosorbent assay
FBS Fasting blood sugar
FFAs Free fatty acids
HbA1c Hemoglobin A1c
HC Hip circumference
HDL‑C High‑density lipoprotein cholesterol
HTN Hypertension
IFCC International Federation of Clinical Chemistry
IPAQ‑SF International physical activity questionnaire‑short form
IR Insulin resistance
LPS Lipopolysaccharide
MAFLD Metabolic associated fatty liver disease
MET Metabolic equivalent of task
Mets Metabolic syndrome
MCP‑1 Monocyte chemoattractant protein
mHDL Monocyte to high‑density lipoprotein cholesterol ratio
MLR Monocyte to lymphocyte ratio
MUFA Monounsaturated fatty acids
NAFLD Non‑alcoholic fatty liver disease
NLR Neutrophil to lymphocyte ratio
NNT Number needed to treat
PCOS Polycystic ovary syndrome
PLR Platelets to to lymphocyte ratio
RAS Random Allocation Software
RCT Randomized clinical trial
SD Standard deviation
SBP Systolic blood pressure
SIRI Systemic inflammation response index
T2DM Type 2 diabetes mellitus
TLR‑4 Toll‑like receptors‑4
TNF‑α Tumor necrosis factor‑α
WBC White blood cell
WC Waist circumference
WHR Waist to hip ratio
WHtR Waist to height ratio
Author contributions
The authors’ responsibilities were as follows: FR and TB help in data collection;
MK contributed in patient selection; FR and SA wrote the original paper; FR
and MEM did statistical analysis; MEM and HT contributed to the conception
of the article as well as to the final revision of the manuscript. All authors read
and approved the final version of the manuscript.
Funding
This study was funded by the ‘Research Vice‑Chancellor’ of Tabriz University
of Medical Sciences, Tabriz, Iran. This paper is a part of the data obtained from
an MSc dissertation submitted to Tabriz University of Medical Sciences (Farnaz
Rooholahzadegan).
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 12 of 14
Rooholahzadeganetal. Nutrition & Metabolism (2023) 20:11
Availability of data and materials
The datasets used and/or analyzed during the current study are available from
the corresponding author on a reasonable request.
Declarations
Ethics approval and consent to participate
All procedures performed in this study were in accordance with the ethical
standards of the Ethics Committee of Tabriz University of Medical Science.
In this study all subjects signed a consent form and the study protocol was
approved by the ethical committee of Tabriz University of Medical Sciences
(Ethics code: TBZMED. REC. 1398.741) and also registered in the Iranian Regis‑
try of Clinical Trials (IRCT20100209003320N17).
Competing interests
The authors declare that they have no competing interests.
Received: 16 September 2022 Accepted: 8 February 2023
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