Consumption of extra virgin olive oil improves body composition and blood pressure in women with excess body fat: a randomized, double-blinded, placebo-controlled clinical trial

Abstract

Purpose:
Despite the fact that extra virgin olive oil (EVOO) is widely used in obese individuals to treat cardiovascular diseases, the role of EVOO on weight/fat reduction remains unclear. We investigated the effects of energy-restricted diet containing EVOO on body composition and metabolic disruptions related to obesity.

Methods:
This is a randomized, double-blinded, placebo-controlled clinical trial in which 41 adult women with excess body fat (mean ± SD 27.0 ± 0.9 year old, 46.8 ± 0.6% of total body fat) received daily high-fat breakfasts containing 25 mL of soybean oil (control group, n = 20) or EVOO (EVOO group, n = 21) during nine consecutive weeks. Breakfasts were part of an energy-restricted normal-fat diets (-2090 kJ, ~32%E from fat). Anthropometric and dual-energy X-ray absorptiometry were assessed, and fasting blood was collected on the first and last day of the experiment.

Results:
Fat loss was ~80% higher on EVOO compared to the control group (mean ± SE: -2.4 ± 0.3 kg vs. -1.3 ± 0.4 kg, P = 0.037). EVOO also reduced diastolic blood pressure when compared to control (-5.1 ± 1.6 mmHg vs. +0.3 ± 1.2 mmHg, P = 0.011). Within-group differences (P < 0.050) were observed for HDL-c (-2.9 ± 1.2 mmol/L) and IL-10 (+0.9 ± 0.1 pg/mL) in control group, and for serum creatinine (+0.04 ± 0.01 µmol/L) and alkaline phosphatase (-3.3 ± 1.8 IU/L) in the EVOO group. There was also a trend for IL-1β EVOO reduction (-0.3 ± 0.1 pg/mL, P = 0.060).

Conclusion:
EVOO consumption reduced body fat and improved blood pressure. Our results indicate that EVOO should be included into energy-restricted programs for obesity treatment.

Full text

Vol.:(0123456789)
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Eur J Nutr (2018) 57:2445–2455
https://doi.org/10.1007/s00394-017-1517-9
ORIGINAL CONTRIBUTION
Consumption ofextra virgin olive oil improves body composition
andblood pressure inwomen withexcess body fat: arandomized,
double‑blinded, placebo‑controlled clinical trial
FláviaGalvãoCândido1 · FláviaXavierValente1· LaísEmiliadaSilva1·
OlíviaGonçalvesLeãoCoelho1· Maria do CarmoGouveiaPeluzio1·
Rita de CássiaGonçalvesAlfenas1
Received: 10 March 2017 / Accepted: 23 July 2017 / Published online: 14 August 2017
© Springer-Verlag GmbH Germany 2017
serum creatinine (+0.04±0.01µmol/L) and alkaline phos-
phatase (−3.3±1.8IU/L) in the EVOO group. There was
also a trend for IL-1β EVOO reduction (−0.3±0.1pg/mL,
P=0.060).
Conclusion EVOO consumption reduced body fat and
improved blood pressure. Our results indicate that EVOO
should be included into energy-restricted programs for obe-
sity treatment.
Keywords Extra virgin olive oil· Soybean oil· Body fat·
Blood pressure· Adiposity· Monounsaturated fatty acid
Introduction
Obesity results from complex interactions between genetic
and lifestyle factors. The consumption of high-fat diets has
been considered one of the main factors predisposing fat
gain [1–3]. However, the role of dietary fat on obesity patho-
genesis remains unclear.
Extra virgin olive oil (EVOO) is a high-quality oil rich in
monounsaturated oleic acid (55–85% of fatty acid content),
which contains more than 230 chemical constituents with
antioxidant activity such as vitamin E, carotenoids, and phe-
nolic compounds [4]. Due to the well-established beneficial
effects of that oil over CVD risk [5–8] and the strong associ-
ation between CVD and excess body fat, the consumption of
energy-restricted diet containing EVOO has been adopted in
weight loss programs. However, the benefits of EVOO over
CVD have been inadvertently extrapolated for weight/fat
loss promotion without adequate scientific evidence [9, 10].
The current hypothesis that EVOO could also contribute
to weight/fat loss is mostly based on observational evidence,
demonstrating that the consumption of Mediterranean diet
rich in olive oil was significantly less likely to favor obesity
Abstract
Purpose Despite the fact that extra virgin olive oil (EVOO)
is widely used in obese individuals to treat cardiovascular
diseases, the role of EVOO on weight/fat reduction remains
unclear. We investigated the effects of energy-restricted diet
containing EVOO on body composition and metabolic dis-
ruptions related to obesity.
Methods This is a randomized, double-blinded, placebo-
controlled clinical trial in which 41 adult women with excess
body fat (mean±SD 27.0±0.9 year old, 46.8±0.6% of
total body fat) received daily high-fat breakfasts containing
25mL of soybean oil (control group, n=20) or EVOO
(EVOO group, n=21) during nine consecutive weeks.
Breakfasts were part of an energy-restricted normal-fat
diets (−2090kJ,~32%E from fat). Anthropometric and
dual-energy X-ray absorptiometry were assessed, and
fasting blood was collected on the first and last day of the
experiment.
Results Fat loss was~80% higher on EVOO com-
pared to the control group (mean±SE: −2.4±0.3 kg vs.
−1.3±0.4kg, P=0.037). EVOO also reduced diastolic
blood pressure when compared to control (–5.1±1.6mmHg
vs. +0.3±1.2mmHg, P=0.011). Within-group differences
(P<0.050) were observed for HDL-c (−2.9±1.2mmol/L)
and IL-10 (+0.9±0.1pg/mL) in control group, and for
Electronic supplementary material The online version
of this article (doi:10.1007/s00394-017-1517-9) contains
supplementary material, which is available to authorized users.
* Flávia Galvão Cândido
flaviagcandido@hotmail.com
1 Departamento de Nutrição e Saúde, Universidade
Federal de Viçosa, Avenida PH Rolfs, s/n, Viçosa,
MinasGeraisCEP:36570-900, Brazil

2446 Eur J Nutr (2018) 57:2445–2455
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[11–13]. Results from these observational studies are dif-
ficult to interpret because habitual use of olive oil in salads
and vegetable-based dishes within the Mediterranean diet
is also associated with the consumption of other functional
low-density foods [10, 14]. Furthermore, randomized clini-
cal trials about this topic are scarce, and presented inconclu-
sive and controversial results [10, 15]. In some clinical trials,
the great discrepancy in the dietary intervention applied to
the control and test groups may have favored the reduction
in body weight/fat in response to olive oil consumption [16,
17]. On the other hand, other clinical trials reported no influ-
ence of olive oil on body weight/fat [18] or even an increase
in abdominal obesity [19] when it was incorporated into
Mediterranean diet. When consumed associated with an
energy-restricted non-Mediterranean diet, olive oil reduced
less body weight than medium-chain triacylglycerol—MCT
[20].
Despite the fact that the incorporation of good fat source
into energy-restricted diets can improve palatability and
favor compliance of the traditional energy-restricted low-
fat diet [21], there is no clear evidence supporting the effect
of EVOO to improve body weight/fat loss. Therefore, we
investigated the effect of the consumption of EVOO into an
energy-restricted non-Mediterranean diet on body weight/
fat. Additionally, we assessed the role of EVOO on systemic
inflammation, cardiovascular, hepatic and renal functions,
which can be impaired due to lipotoxicity.
Methods
Subjects
Seven hundred fifty-three women were assessed for eli-
gibility through local advertisements and seventy-seven
apparently healthy middle-aged women (19–41 years, BMI
between 26 and 35kg/m2) met the inclusion criteria and
were allocated to study groups (Fig.1). Potential subjects
had excess body fat (>32%); habitually used soybean oil
as cooking oil; were nonsmoker, non-pregnant, and non-
lactating. The exclusion criteria were the followings: alcohol
consumption (>15g of ethanol/day), elite athletes (>10h of
exercise/week), habitual consumption of olive oil (more than
8mL/day), recent changes (<3 months) in diet or physical
activities habits, use of supplements or drugs except con-
traceptive ones, the presence of food allergy/intolerance or
aversion to tested ingredients, gastrointestinal diseases or
other acute or chronic diseases besides obesity.
From the 77 initially recruited women, 16 dropped out
before starting the intervention. Sixty-one eligible women
were included in the study, 51 completed the adopted pro-
tocol, and 41 were included in the analyses. The reasons by
which ten women were not included in the final analyses
were the following: pregnancy (n=1), secondary pathologi-
cal events not related to the intervention (n=6) and drop
out (n=3). Because all subjects which finished the study
follow the entire study protocol, there was no exclusion due
to lack of compliance in this study. Power calculation was
performed retrospectively [22] and indicated that 21 sub-
jects were necessary to detect an increment of 1.09kg in
total body fat loss presented by EVOO group (mean±stand-
ard deviation of change in body fat loss of overall subjects;
1.9±1.8kg; statistical power=90%; α=5%). An incre-
ment of~1kg in body fat loss is relevant considering the
duration of this study and this preventive nature [23].
All recruited participants gave written consent after
receiving verbal and written information about the experi-
ment. The study protocol was approved by the Ethics Com-
mittee of Universidade Federal de Viçosa (protocol number:
892.467/2014), conducted in accordance with 1964 Declara-
tion of Helsinki and its latter amendments, and registered at
http://www.ensaiosclinicos.gov.br/ (identifier: RBR-7z358j).
Experimental design
This was a double-blinded, randomized, parallel, pla-
cebo-controlled clinical trial for nine consecutive weeks
(±5days), in which subjects were randomly assigned to
control (soybean oil) or interventional (EVOO) groups. The
tolerance of±5days to end the experiment was required
to prevent impairment on anthropometric/body composi-
tion parameters assessments due to hormonal changes. The
allocation on the control or interventional groups was made
using the block randomization technique [24] and was con-
cealed from the investigators. High-fat drinks were served
into colored cups to avoid visual identification of the type
of drink tested. There was no description or dietary infor-
mation about the breakfasts on those cups. Therefore, nei-
ther subjects nor investigators were aware of the treatment
assignments.
One week before beginning the trial, selected women
refrained from eating olive oil, were instructed to not con-
sume alcohol beverages and to maintain their usual dietary
and physical activity habits. A standard dinner (2508kJ, car-
bohydrate: 62 E%, fat: 29.4 E%, protein: 8.5 E%) was con-
sumed the night before the test day. Women were reported to
laboratory in a fasting state for anthropometric, body com-
position, and blood pressure assessments at baseline and on
the last day of the experiment. Inclusion in the study was
postponed if women presented any symptoms of inflamma-
tion or intestinal disorder. After the assessments, subjects
underwent blood collection and consumed a high-fat break-
fast containing 25mL of soybean oil or EVOO for breakfast.
The amount of oil (25mL) added to the drinks was based
on the range of olive oil usually consumed by Mediterra-
nean population (25–50mL/day) [25] without exceeding the

2447Eur J Nutr (2018) 57:2445–2455
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fat consumption recommendations [26]. During the other
study days, high-fat breakfasts were daily provided in the
laboratory as part of an energy-restricted non-Mediterranean
diet and women were released from the laboratory to follow
the prescribed diet in free-living conditions. Habitual food
intake, physical activity level, and prescribed diet compli-
ance were also assessed (Suppl. Figure1).
Breakfasts
Extra virgin olive oil (Andorinha®, Sovena S.A., Algés, Por-
tugal) and soybean oil (Corcovado, Archer Daniels Mid-
land, Uberlândia, Brazil) were used to prepare the high-fat
drinks (300mL of a milk-derived flavored drink contain-
ing 25mL of the previously mentioned oils) as part of a
breakfast. Both oils were protected from light and heat until
their consumption. The high-fat drinks were matched in all
ingredients except for the type of oil used to prepare them.
During all the experimental period, subjects attended the
laboratory daily on weekdays to have the breakfasts accord-
ing to the allocated group. On weekends, identical breakfasts
containing the test oils were provided to be consumed at
home. Besides the high-fat drinks, two low-fat cookies were
also offered for breakfast. A rotating menu of six break-
fast flavors, with very similar nutritional composition, was
prepared to avoid monotony and to improve compliance to
the study protocol (Suppl. Table1). Protocol compliance on
weekends was assessed by asking subjects about the break-
fast consumption and by the return of the packages in which
the breakfasts were taken. Subjects were not informed about
the exclusion of the study if they did not follow the protocol
to guarantee the confidence of the information.
Fig. 1 CONSORT diagram
showing the flow of participants
through each stage of the trial.
CONSORT Consolidated Stand-
ards of Reporting Trials
Analysis
Allocated to olive oil intervention (n= 38)
♦Received allocated intervention (n=33)
♦Did not receive allocated intervention (n= 5)
♦Lost to follow-up(n=0)
♦Discontinued intervention (n=7)
-Secondary pathological events (n= 3)
-Drop out due to personal reasons (n= 3)
Allocated to control intervention (n= 39)
♦Received allocated intervention (n=28)
♦Did not receive allocated intervention (n= 11)
Excluded (n= 675)
♦Not meeting inclusion criteria (n= 519)
♦Declined to participate (n= 122)
♦Other reasons (n= 34)
Follow-U
p
Analyzed (n= 21)
♦Did not include from analysis
-Pregnancy(n= 1)
-Secondary pathological events (n= 2)
-Drop out due to personal reasons (n = 2)
Analyzed (n= 20)
♦Did not include from analysis
-Secondary pathological events (n=4)
-Drop out due to personal reasons (n=1)
Enrollment Assessed for eligibility (n= 752)
♦Lost to follow-up (n= 0)
♦Discontinued intervention
-Secondary pathological events (n= 3)
Allocation Randomized (n= 77)

2448 Eur J Nutr (2018) 57:2445–2455
1 3
EVOO and soybean oil fatty acids profile were performed
in triplicate. Fatty acid composition of EVOO was assessed
in laboratory after esterification [27] by gas chromatography
(GC) [28] (Suppl. Table1).
Dietary assessments
Energy-restricted nutritionally balanced diets were individu-
ally prescribed by a single dietitian. The type of foods pre-
scribed and the macronutrient distribution were maintained
during the intervention to reduce the influence of prescribed
diets beyond fats on results. There were no differences on
energy and macronutrient content of prescribed diet between
groups (7836.7±897.4kJ, carbohydrate: 49.0±2.8% E,
fat: 31.8±2.85% E, protein: 19.1±2.4% E). No other high
MUFA food besides the 25mL of EVOO for the EVOO
group was prescribed, and a food substitution list was used
to subsidize food choices.
Total energy requirements were estimated according to
total energy expenditure for overweight/obese women [26].
Then, caloric restriction (−2090kJ/day) was applied. Physi-
cal activity levels [29] were used to obtain physical activ-
ity coefficients (1.00 for sedentary or 1.16 for low-active
individuals) [26]. Three non-consecutive days (2 weekdays
and 1 weekend day) 24-h food records were applied to
assess food intake on the week before baseline, and during
the experimental period. Macro- and micronutrient intakes
were analyzed by a single dietitian using DietPro software
(version 5.2i, Agromídia, MG, Brazil), and were based on
reliable composition tables [30–32].
Anthropometric, body composition, andblood pressure
measurements
Anthropometric measurements were assessed by a single
investigator. Body weight was measured on a digital platform
scale with a resolution of 0.5kg (Toledo®, Model 2096PP/2,
SP, Brazil), while subjects were barefoot and wearing light-
weight clothing. Height was measured to the nearest 0.1cm
using a wall-mounted stadiometer (Wiso, Chapecó, SC, Bra-
zil). BMI was calculated by dividing body (kg) by height
(m) squared. Waist, hip, neck, and thigh circumferences, as
well as sagittal abdominal diameter, were measured in trip-
licate as described by Vasques etal. [33]. The average of
the two nearest values of the three collected measurements
was recorded. Waist circumference and sagittal abdominal
diameter were measured in the midpoint between the last
rib and iliac crest. Waist/hip, and conicity index (CI) were
calculated following the formula: CI=[waist circumference
(m)]/[0.109 √(body weight (kg)/height (m))] [34]. Blood
pressure was measured by an automatic Omron HEM-7200
device (Omron Inc., Dalian, China) in both arms, according
to Mancia etal. [35].
Dual-energy X-ray absorptiometry scan (DXA) (model
Prodigy Advance, GE Healthcare Inc., Waukesha, WI) was
performed to assess changes in body composition according
to manufacturer’s instructions. Values of lean mass, total
body fat, and fat distribution (truncal, gynoid, and android
regions) were obtained.
Metabolic biomarkers
Antecubital blood samples were collected in the fasting state
(12h). Serum (serum gel tubes) and plasma (EDTA tubes)
samples were separated from whole blood by centrifugation
(3500rpm, 4°C, 15min) and immediately frozen at −80°C
until analyses. Serum glucose, triglycerides (TG), total cho-
lesterol, high-density lipoprotein cholesterol (HDL-c), low-
density lipoprotein cholesterol (LDL-c), uric acid, urea,
creatinine, alkaline phosphatase (AP), γ-glutamyltransferase
(Gamma GT), aspartate amino transferase (AST), and ala-
nine amino transferase (ALT) were quantified by an auto-
mated analyzer system (BS-200™ Chemistry Analyzer,
Mindray) using available commercial colorimetric assay
kits (K802, K117, K083, K071, K088, K139, K056, K067,
K021, K080, K048, and K049, respectively; Bioclin®, MG,
Brazil). The serum very-low-density lipoprotein cholesterol
(VLDL-c) was calculated using Friedewald etal. equations
[36]. Serum insulin was quantified using eletroquimiolumi-
nescence method (Elecsys-Modular E-170, Roche Diagnos-
tics Systems). The homeostasis model assessment of insulin
resistance (HOMA-IR) was calculated to estimate insulin
resistance according to the equation proposed by Matthews
etal. [37]. atherogenic index (TG/HDL-c ratio) were also
calculated [38].
Flow cytometry analysis was performed using a BD
FACS Verse™ flow cytometer (BD Biosciences). Interleu-
kin-8 (IL-8), interleukin-1β (IL-1β), interleukin-6 (IL-6),
interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α),
and interleukin-12p70 (IL-12p70) plasma concentrations
were measured using commercial kit (Cytometric Bead
Array CBA Human Inflammatory Cytokines Kit, BD Bio-
sciences) according to the manufacturers’ instructions. Data
were analyzed using the FCAP Array Software v3.0 (BD
Biosciences).
Statistical analysis
Data were typed by two independent investigators to ensure
data reliability. Group data were coded before the data analy-
ses for blindness. Per-protocol analyses were performed due
to the large number of participants who did not complete
the intervention after being randomized. Statistical analy-
ses were carried out on SPSS 20 for Windows (SPSS, Inc.,
Chicago, IL, USA). Data are expressed as mean±standard
deviation (SD) for descriptive variables or mean±standard

2449Eur J Nutr (2018) 57:2445–2455
1 3
error (SE) and median (interquartile range) for comparative
data. Individual outlier values were excluded before analy-
ses. The thresholds for lower and upper outliers were defined
as follows: lower thresholds=lower quartile—(1.5 × inter-
quartile range) and upper threshold=upper quartile+(1.5
× interquartile range). Data normality and homoscedasticity
were assessed by Shapiro–Wilk and Levene’s tests, respec-
tively. Paired Student’s t test or Wilcoxon signed-rank test
were used to assess within group differences. Differences
between groups were assessed over absolute delta (Δ) values
(9weeks—baseline) by Student’s t test or Mann–Whitney U
signed-rank test. Pearson’s or Spearman’s correlation coef-
ficients were used to assess the relation between fat reduc-
tion and metabolic biomarkers. A 5% α level of significance
was adopted.
Results
Subjects
Forty-one women completed the study protocol and were
included in the analyses. Participants were 27.0±0.9
years old, presented 46.8±0.6% of total body fat, and
30.2±0.4kg/m2 of BMI (overweight: n=23 or 56.1%;
obese: n=18 or 43.9%). There were no significant between-
group differences in baseline food intake and in all anthro-
pometric, body composition, blood pressure, and metabolic
variables assessed in this study, except for diastolic blood
pressure and TNF-α which EVOO presented higher values
(Table1). None of the participants had systolic blood pres-
sure higher than 139mmHg and only one EVOO group par-
ticipant had diastolic blood pressure ranging from 90 to 99
(first state of hypertension). Despite the fact that none of
the participants showed symptoms of acute inflammation
during the test days, five of them presented a clear inflam-
matory cytokines profile (TNF-α and IL-6 values were twice
as higher as the highest values showed by the total sample)
and were excluded from final analysis. Eight participants
from both groups presented TNF-α concentration below the
detection limits of the assay kit. Six participants from the
control group and five from the EVOO group had no detect-
able concentrations for IL-1β. That did not occur for the
other cytokines.
Dietary assessments
As expected, food intake analyses during experiment period
showed reduction in energy and macronutrients intake values
compared to baseline in both groups due to energy restric-
tion. Dietary intake during the experiment only differed
between groups for C18:1, C18:2, total monounsaturated
fatty acids, and total polyunsaturated fatty acids (P<0.001),
reflecting the differences in the fatty acid profile of the sup-
plemented oils (Table2).
Anthropometric, body composition, andblood pressure
measurements
Body weight (−1.70±0.47 kg 95% CI −2.69 to −0.72
vs. −2.75±0.38 kg 95% CI −3.54 to −1.95 for con-
trol and EVOO groups, respectively; Pinter=0.094) and
BMI (−0.64±0.17kg/m2, 95% CI −1.00 to −0.28 vs.
−1.06±0.15kg/m2 95% CI −1.37 to −0.75; Pinter=0.072)
reduced with time in both groups due to energy restriction.
However, EVOO presented a greater reduction on total body
fat than control (−1.30±0.40kg 95% CI −2.21 to −0.44
vs. −2.4±0.3kg 95% CI −3.1 to −1.73, Pinter=0.037).
Fat loss was~80% higher on EVOO compared to control
group. In addition, EVOO reduced diastolic blood pres-
sure (+0.25±1.16 mmHg, 95% CI −2.18 to 2.68 vs.
−5.05±1.60mmHg 95% CI −8.39 to −1.70; Pinter=0.011).
There were no differences between groups in systolic blood
pressure (−3.65±1.54mmHg 95% CI −6.87 to −0.44 vs.
−3.91±1.88mmHg 95% CI −7.83 to 0.02; Pinter=0.918)
(Fig.2).
There was no difference between groups for the other
variables. As expected all of the evaluated anthropomet-
ric variables, except waist/thigh ratio reduced with time
in control and EVOO groups. In addition, both groups
showed weight reductions on total fat and specific fat
mass sites (truncal, gynoid, and android regions), but
not on lean mass (Suppl. Table2). Total body lean mass
Table 1 Baseline characteristics of study subjects according to
experimental groups
Values are mean±SE or median (interquartile range). Waist circum-
ference values were measured at umbilical level
BMI body mass index, S/LA number of sedentary and low-active indi-
vidual ratios (28), SAD Sagittal abdominal diameter, MUFA monoun-
saturated fatty acids, PUFA polyunsaturated fatty acids, SFA saturated
fatty acids
Control Extra virgin olive oil
Subjects (n) 20.0 21.0
Age (years) 27.2±6.1 26.8±5.0
Physical activity (S/LA) 6.00/14.0 3.00/18.0
Systolic blood pressure (mmHg) 109±2.10 115±2.40
Diastolic blood pressure (mmHg) 67.5±1.50 74.5±1.90
Body weight (kg) 77.6±2.00 77.6 (13.2)
BMI (kg/m2) 29.7±0.60 30.5±0.60
Waist circumference (cm) 97.7±1.60 98.9±1.60
SAD (cm) 19.6±0.50 19.7±0.40
Total body fat (kg) 37.0±1.40 34.4 (11.2)
Total body fat percentage (%) 46.6±0.70 47.0±0.90
Total lean mass (%) 49.4±0.84 49.0±0.98

2450 Eur J Nutr (2018) 57:2445–2455
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Table 2 Dietary assessments at baseline and change from baseline (95% CI) according to experimental groups
Values are mean±SE or median (interquartile range)
SFA saturated fatty acids, MUFA monounsaturated fatty acids, PUFA polyunsaturated fatty acids, C18:1 oleic fatty acid, C18:2 linoleic fatty
acid, PInter between-group Δ values (9week—baseline) by Student’s t test or Mann–Whitney U signed-rank test, P>0.050
Metabolic biomarkers Control (n=20) Extra virgin olive oil (n=21) PInter
Baseline Δ values 95% CI Baseline Δ values 95% CI
Energy content (kJ) 3565 (2775) −794±184 −1179 to −406 8343±434 −1041±179 − 1417 to − 665 0.342
Carbohydrate (g) 229 (66.7) −24.5±5.66 −36.4 to −12.6 261±16.1 −36.1±5.88 −48.4 to −23.7 0.165
(%E) 50.8±1.58 51.8 (55.2) 21.9 to 159 52.2±1.54 54.6 (74.5) 30.1 to 93.7 0.624
Fiber (g) 19.2±1.50 −0.60±0.72 −2.11 to 0.91 21.0±1.50 −1.67±1.09 −3.95 to 0.61 0.418
Protein (g) 78.2±5.30 −9.66±2.39 −14.7 to −4.65 81.8±3.5 −11.1±2.02 −15.3 to −6.84 0.654
(%E) 16.6±0.79 15.8 (25.2) −21.6 to 37.9 16.8±0.72 18.8 (24.1) 7.06 to 60.7 0.840
Total fat (g) 61.8 (25.6) −2.11 (12.2) −7.96 to 1.82 67.7±5.04 −2.80 (17.1) −10.7 to 0.27 0.708
(%E) 30.1±1.41 23.8 (52.4) −73.2 to 44.3 30.2±1.19 13.7 (59.4) −37.2 to 27.5 0.773
Total SFA (g) 20.1 (12.3) −2.41 (4.42) −5.86 to −1.95 21.1±1.50 −2.60 (4.72) −4.90 to −2.00 0.954
Total MUFA (g) 16.4 (9.11) −1.54±0.64 −2.89 to −1.20 20.2±1.46 4.56 (4.56) 1.53 to 6.04 <0.001
Total PUFA (g) 10.6 (5.18) 5.57 (3.96) 3.24 to 5.82 12.8 (11.2) −2.84 (4.05) −5.30 to −1.32 <0.001
C18:1 (g) 11.7±0.99 0.85±0.42 −0.03 to 1.72 13.8±1.15 6.23 (3.28) 4.00 to 7.49 <0.001
C18:2 (g) 7.49 (3.64) 5.07 (2.99) 3.57 to 5.51 9.67 (5.22) −1.73 (2.55) −3.83 to −0.65 <0.001
Cholesterol (mg) 222±17.0 −37.6±10.0 −58.7 to −16.6 251±20.8 −45.5±13.4 −73.7 to −17.3 0.642
Sodium (mg) 2469±159 −408±79.8 −575 to −240 2168 (1662) −404 (807) −908 to −385 0.234
-3.5
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
ControlEVOO
Changes in body weight (kg)
-1.4
-1.2
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
ControlEVOO
-3.0
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
ControlEVOO
Changes in total body fat
(kg)
-7.0
-6.0
-5.0
-4.0
-3.0
-2.0
-1.0
0.0
ControlEVOO
Changes in systolic blood
pressure (mmHg)
-8.0
-6.0
-4.0
-2.0
0.0
2.0
ControlEVOO
Changes
diastolic blood
pressure (mmHg)
*
*
*
*
*
*
P Inter= 0.094 P Inter= 0.072 P Inter= 0.037
§
*
abc
de
*
P Inter= 0.011
P Inter= 0.918
§
Fig. 2 Mean ± SE body weight (a), body mass index – BMI (b),
total body fat (c), systolic blood pressure (d), and diastolic blood
pressure (e) changes (Δ values= 9 week values – baseline values).
Energy-restricted nutritionally balanced diets (−2090kJ/d) contain-
ing 25mL of soybean oil (control group, n=20) or extra virgin olive
oil – EVOO (EVOO group, n=21) were prescribed. *Within-group
significant differences (paired Student’s t test or Wilcoxon signed-
rank test, P<0.05). §PInter values indicate between groups differences
(Student’s t test or Mann–Whitney U signed-rank test, P<0.050)

2451Eur J Nutr (2018) 57:2445–2455
1 3
percentage was not affected in the control group, but
there was an increase in EVOO group (0.68±0.46%
95% CI −0.30 to 1.65 vs. 1.45±0.36 95% CI 0.69–2.20;
Pinter=0.195).
Metabolic biomarkers
Serum glucose reduced in both groups after the intervention
without a significant difference between groups (P=0.811).
Despite no between-group changes in metabolic biomark-
ers, HDL-c reduced and IL-10 increased only in the control
group. On the other hand, EVOO was the only group in
which creatinine increased and alkaline phosphatase reduced
(Table3). There as positive correlation between changes
in total body fat and changes in alkaline phosphatase
(R2=0.488, P=0.005) and negative correlation between
changes in total body fat and changes in serum creatinine
(R2=−0.360, P=0.021).
Discussion
This study was design to assess the effects of EVOO incor-
porated into an energy-restricted non-Mediterranean diet
program on body weight, body composition and metabolic
biomarkers in women with excess body fat. The main find-
ing of the present study is that the consumption of EVOO
increases total fat loss and reduces diastolic blood pressure
compared to the control soybean oil group. To the best of
our knowledge, this paper provides the first clinical evi-
dence that EVOO consumption increases body fat loss due
to energy-restricted program even when not incorporated
into a Mediterranean diet. Analysis of food consumption
during the experiment demonstrated that our high-fat break-
fasts significantly changed daily consumption of dietary fatty
acids. EVOO group increased body fat loss, which could be
considered independent of a greater caloric restriction in
EVOO than control group once difference between groups in
energy intake was not significant and insufficient to explain
Table 3 Metabolic biomarkers at baseline and change from baseline (95% CI) according to experimental groups
Values are mean±SE or median (interquartile range)
HOMA-IR homeostasis model assessment of insulin resistance [36], HDL-c high-density lipoprotein cholesterol, LDL-c low-density lipopro-
tein cholesterol, ALP alkaline phosphatase, AP alkaline phosphatase, Gamma GT γ-glutamyltransferase, AST aspartate amino transferase, ALT
alanine amino transferase, IL-8 interleukin-8, IL-1β interleukin-1β, IL-6 interleukin-6, IL-10 interleukin-10, TNF-α tumor necrosis factor-α, IL-
12p70 interleukin-12p70, PInter between-group Δ values (9week—baseline) are not significantly different (Student’s t test or Mann–Whitney U
signed-rank test, P>0.05)
Metabolic biomarkers Control (n=20) Extra virgin olive oil (n=21) PInter
Baseline Δ values 95% CI Baseline Δ values 95% CI
Glucose (mmol/L) 4.76±0.09 −0.13±0.05 −0.23 to −0.02 4.86 (0.50) −0.11 (0.39) −0.37 to −0.04 0.811
Insulin (pmol/L) 7.90 (3.80) 3.82 (35.6) −0.56 to 27.0 8.10 (4.20) −4.31±5.90 −16.7 to 8.20 0.060
HOMA−IR 1.61 (0.76) 0.08 (1.15) −0.08 to 0.76 1.92 (1.14) −0.19±0.22 −0.64 to 0.26 0.054
Triglycerides (mmol/L) 0.98±0.09 −0.02 (0.28) −0.24 to 0.06 1.27±0.13 −0.07±0.07 −0.23 to 0.09 0.579
Total cholesterol (mmol/L) 4.26±0.19 −0.14±0.08 −0.30 to 0.02 4.45±0.20 −0.20±0.12 −0.44 to 0.05 0.671
HDL-c (mmol/L) 1.19±0.06 −0.07±0.03 −0.14 to −0.01 1.31±0.07 −0.03±0.03 −0.10 to 0.03 0.385
LDL-c (mmol/L) 2.42±0.15 −0.06±0.06 −0.18 to 0.06 2.52±0.15 −0.04±0.08 −0.21 to 0.12 0.832
Triglycerides/HDL−c 0.90±0.12 0.00±0.13 −0.26 to 0.27 0.79 (0.55) 0.10±0.10 −0.11 to 0.31 0.548
Uric acid (µmol/L) 206±7.73 2.38±7.14 −11.9 to 16.7 209±8.92 −2.97±5.95 −14.9 to 9.52 0.579
Creatinine (µmol/L) 51.3±0.88 −0.00±1.77 −2.65 to 2.65 50.4±1.77 3.54±0.88 1.15 to 5.75 0.057
AP (IU/L) 61.1±3.47 −1.68±2.05 −5.98 to 2.62 63.7±4.89 −3.26±1.78 −7.00 to 0.47 0.564
Gamma GT (IU/L) 21.9±0.60 0.11±0.52 −0.98 to 1.20 19.1±1.43 −0.24±0.70 −1.72 to 1.25 0.691
AST (IU/L) 34.0±1.56 −0.95±2.09 −5.35 to 3.45 30.0 (14.0) −0.24±1.51 −3.40 to 2.92 0.782
ALT (IU/L) 16.0 (7.25) −2.06±1.06 −4.30 to 0.19 17.7±1.84 0.16±1.38 −2.74 to 3.06 0.219
IL-8 (pg/mL) 6.83±0.51 0.61±0.51 −0.48 to 1.69 8.07±0.78 0.27±0.70 −1.22 to 1.77 0.706
IL-1β(pg/mL) 0.98±0.25 0.06±0.23 −0.50 to 0.61 1.24±0.29 −0.28±0.14 −0.62 to 0.06 0.252
IL-6 (pg/mL) 1.74±0.25 −0.03±0.35 −0.80 to 0.73 1.76±0.22 0.16±0.26 −0.39 to 0.71 0.655
IL-10 (pg/mL) 0.86±0.08 0.189±0.08 0.01 to 0.37 1.11±0.14 0.05±0.09 −0.14 to 0.24 0.259
TNF- (pg/mL) 0.25±0.10 0.00 (0.00) −1.96 to 3.13 0.61 (0.45) 0.09±0.29 −0.65 to 0.84 0.905
IL-12p70 (pg/mL) 2.08±0.45 −0.14±0.47 −1.17 to 0.88 2.15±0.39 −0.10±0.31 −0.77 to 0.56 0.942
IL-10/IL-6 (pg/mL) 2.15±0.39 −0.39±0.29 −1.01 to 0.25 1.63±0.21 0.12±0.28 −0.49 to 0.72 0.227

2452 Eur J Nutr (2018) 57:2445–2455
1 3
such increase [39]. Furthermore, our results show that while
IL-10 increased only in the control group, HDL-c concentra-
tions reduced in that same group. On the other hand, serum
creatinine increased, alkaline phosphatase reduced, and
there was a trend for IL-1β reduction in the EVOO group
along the nine experimental weeks.
It has been widely suggested that the consumption of a
Mediterranean diet rich in olive oil can prevent type 2 dia-
betes mellitus [40, 41] metabolic syndrome [40] and obesity
[17, 40]. However, randomized clinical trials in which the
effect of olive oil on body weight/fat was investigated are
scarce and presented conflicting results [18–20, 42]. In a
recent study [42] involving 7447 asymptomatic high-CVD
risk individuals, daily consumption of 50mL of EVOO for
4.8years associated with an unrestricted-calorie, high-vege-
table Mediterranean diet reduced body weight and promoted
less central adiposity gain compared with the consumption
of a low-fat diet. In our study, the daily consumption of
energy-restricted normal-fat diet containing 25mL of EVOO
reduced total body fat compared to 25mL/day of soybean
oil. Additionally, to the aforementioned study, our findings
support the prescription of EVOO not only for preventing
weight gain, but also for promoting body weight/fat loss.
The current hypothesis that EVOO could improve body
composition was mainly based in the effect of oleic acid
(C18:1) on stearoyl-CoA desaturase 1 (SCD1) [11]. This
enzyme catalyzes a key step in the endogenous biosynthesis
of MUFA from saturated fatty acids. The preferential sub-
strates for its action are palmitic acid and stearic acid, which
are converted by SCD1 into palmitoleic acid and oleic acid,
respectively [43]. The influence of increased SCD1 activity
on obesity is supported by studies using mice with natural
or SCD1-direct mutations. SCD1-deficient mice consume
25% more food but accumulate less fat and are consider-
ably thinner than normal mice [44, 45]. In addition, SCD1-
deficient animals consume more oxygen and have higher
rates of β-oxidation in liver and fat tissue [46]. The lack of
SCD1 also beneficially modulates the expression and activ-
ity of some genes related to adiposity [47]. According to
this hypothesis, SCD1 activity is regulated by the amount
of substrate and final product. Thus, while consumption of
the saturated fatty acids palmitic and stearic acid acts as sub-
strate stimulating SCD1 action and favoring obesity, oleic
acid down regulates SCD1 activity favoring weight loss [11].
The effect of EVOO consumption on SCD1 expression and
activity must be investigated in metagenomic studies.
In our study, EVOO significantly reduced (~5mmHg)
diastolic blood pressure compared to the control (soybean
oil). Soybean oil could be considered a good control for
assessing blood pressure due to its little effect on that vari-
able [48]. Therefore, despite the differences in baseline val-
ues observed in diastolic blood pressure, our results suggest
that EVOO contribute to hypertension control. The role of
EVOO in reducing blood pressure is supported by a grow-
ing body of scientific evidence [46–49]. Despite the fact
that minor components characteristic of olive oil could con-
tribute to the cardioprotective activity of EVOO, such as
a-tocopherol, polyphenols, and other phenolic compounds,
Terés etal. [49] demonstrated that its high oleic acid con-
tent is responsible for the antihypertensive effects of olive
oil consumption. This effect is likely to be attributed to the
incorporation of oleic acid into cell membranes, which regu-
lates membrane lipid structure in such a way as to control
G protein-mediated signaling, causing a reduction in blood
pressure [49].
There is still no consensus about the role of EVOO
on dyslipidemia. While some studies reported beneficial
increase in HDL-c [49, 50] and reduction in LDL-c [51],
others showed no significant changes in lipid profile [47,
52–55]. In our study, EVOO presented cholesterol-neutral
effect, since HDL-c reduced in the control group at the
end of the experiment. Our results corroborated with those
reported by [56], in which there was a decrease in HDL-c
concentrations after the consumption of~50g of soybean
oil and maintenance of HDL-c in response to the consump-
tion of similar amount of olive oil. The authors attributed
the reduction to soybean oil linoleic acid high content and
the maintenanceof HDL-c to the competition between olive
oil chylomicron remnants and HDL for hepatic lipase [56].
Thus, olive oil could prevent HDL-c postprandial decrease,
and maybe contribute for a more favorable lipid profile.
We observed a significant, but no clinically relevant
increase in serum creatinine in the EVOO group. This was
an unexpected result since creatinine was assessed as a bio-
marker of renal function, and we expected that EVOO could
protect kidneys from obese lipotoxicity [57]. However, we
believe that the increase in serum creatinine was a reflect of
lean mass preservation during the study since creatinine is
a lean mass content marker and EVOO was the only group
in which lean mass percentage increased at the end of the
experiment. On the other hand, there was a reduction in
alkaline phosphatase in EVOO. Despite the fact that alka-
line phosphatase is not specific from liver, data from animal
studies provide some evidences that polyphenols from olive
oil could improve liver function by reducing lipid peroxida-
tion in this tissue [58, 59]. Thus, the slight reduction in that
enzyme may reflect and improve in liver function. This result
deserves to be confirmed in individuals with non-alcoholic
fatty liver disease.
In our study, there was a significant increase in IL-10 in
the control group. Soybean oil was provided to the control
group to match fat consumption between groups, but was
responsible for an increased consumption of α-linolenic
acid (C18:3) in that group. Increased consumption of
α-linolenic acid can down-regulate inflammatory pathways
and reduce plasma levels of IL-10 [60]. In turn, EVOO

2453Eur J Nutr (2018) 57:2445–2455
1 3
showed a trend for IL-1β reduction. A very similar effect
of olive oil was observed in another study conducted by
Kremer etal. [61]. In that study, the effect of fish oil vs.
olive oil (placebo) on active human rheumatoid arthri-
tis was investigated. Olive oil consumption led to unex-
pected beneficial effects on the improvement of clinical
aspects of the disease. These benefits were associated with
decreased macrophage IL-1 production although not to
the same extent as the fish oil group [61]. As IL-1β has
potent and vast pro-inflammatory effect over a number of
cells, including macrophages, monocytes, and dendritic
cells [62], the role of EVOO on IL-1β deserves to be fur-
ther explored.
Our study has several strengths, including the rigorous
subjects’ eligibility criteria, the use of DXA for body com-
position assessments, use of double blind protocol, double
digitation of data, controlled breakfasts consumption, and
evaluation of diet compliance. However, the study also has
limitations. This study showed a relatively high attrition
rate due to secondary reasons not related to the study pro-
tocol. Despite the fact that we selected woman with very
high body fat content (~48% at baseline), they were also
young and it is possible that we were not able to detect
the influence of dietary treatment in some metabolic bio-
markers (e.g., some cytokines which were not detected).
Furthermore, women are more prone to present changes in
anthropometric parameters and body compositions due to
menstrual cycle. Despite our efforts to reduce the influence
of water retention, we cannot assure that our results were
not affected by participant hormonal fluctuations. Finally,
the interference of EVOO higher diastolic blood pressure
at baseline in our results cannot be totally neglected.
Conclusion
Daily consumption of 25mL of extra virgin oil (EVOO)
associated with an energy-restricted Western-diet
increased body fat loss and reduced blood pressure.
The beneficial effects of EVOO were independent of an
increase in caloric restriction, indicating a positive direct
role of this oil on adiposity. EVOO also increased serum
creatinine, reduced hepatic alkaline phosphatase, and
tended to reduce IL-1β concentrations. The intriguing
impact of EVOO on SCD1 expression and activity must
be better explored in metagenomic studies.
Acknowledgements We thank Fundação de Amparo à Pesquisa do
Estado de Minas Gerais—FAPEMIG (protocol number: APQ-01877-
1). The Coordenação de Aperfeiçoamento de Pessoal de Nível Supe-
rior—CAPES and Conselho Nacional de Desenvolvimento Científico
e Tecnológico—CNPq for providing research grants to the authors. We
thank Bioclin® for providing biochemical assays kits. These companies
had no role in design, analysis, or writing of this manuscript.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict
of interest.
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