Critical Reviews in Food Science and Nutrition

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The impact of rice bran oil consumption on the

serum lipid profile in adults: a systematic review
and meta-analysis of randomized controlled trials

Behnaz Pourrajab, Mohammad Hassan Sohouli, Ali Amirinejad, Somaye

Fatahi, Mihnea-Alexandru Găman & Farzad Shidfar

To cite this article: Behnaz Pourrajab, Mohammad Hassan Sohouli, Ali Amirinejad, Somaye
Fatahi, Mihnea-Alexandru Găman & Farzad Shidfar (2021): The impact of rice bran oil consumption
on the serum lipid profile in adults: a systematic review and meta-analysis of randomized controlled
trials, Critical Reviews in Food Science and Nutrition, DOI: 10.1080/10408398.2021.1895062

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CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION
https://doi.org/10.1080/10408398.2021.1895062

REVIEW

The impact of rice bran oil consumption on the serum lipid profile in adults: a
systematic review and meta-analysis of randomized controlled trials
Behnaz Pourrajaba,b, Mohammad Hassan Sohoulia,b, Ali Amirinejada, Somaye Fatahib#,
Mihnea-Alexandru G
amanc,d, and Farzad Shidfara
a
Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran; bStudent Research Committee, Faculty
of Public Health Branch, Iran University of Medical Sciences, Tehran Iran; c"Carol Davila" University of Medicine and Pharmacy, Bucharest,
Romania; dCenter of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute, Bucharest, Romania

ABSTRACT KEYWORDS
Dyslipidemia/hyperlipidemia is recognized among the risk factors for lifestyle related diseases. A HDL-c; LDL-c; meta-analysis;
healthy diet, rich in vegetable oils such as rice bran oil (RBO), may aid to improve serum lipid lev- rice bran oil; systematic
els. Thus, the aim of this study was to assess the effects of rice bran oil (RBO) consumption on review; TC; TG;
triacylglycerol
serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein
cholesterol (HDL-c) and triglyceride (TG) levels in adults. The following online databases were
searched for manuscripts published until October 7th 2020: PubMed/Medline, Scopus, Clarivate
Analytics’ Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar. The
effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals
(CI). A total of 8 eligible trials with 14 effect sizes were included in this meta-analysis. Our analysis
revealed that the consumption of RBO significantly decreased serum TC (WMD:
7.29 mg/dL, 95%
CI:
11.32,
3.25, P ¼ 0.000), LDL-c (WMD:
7.62 mg/dL, 95% CI:
11.10,
4.14, P ¼ 0.000) and TG
(WMD:
9.19 mg/dL, 95% CI:
17.99,
0.38, P ¼ 0.041) levels. So, available evidence suggests that
RBO consumption can significantly decrease serum TC, LDL-c and TG levels. Hence, it may play a
role in reducing dyslipidemia/hyperlipidemia risk.

Highlights lipoprotein cholesterol (LDL-C), also known as hypercholes-

terolemia, and often combined with low levels of high-dens-
 Due to its potential nutritional importance and health
ity lipoprotein cholesterol (HDL-C) and elevated TG
benefits, rice bran oil (RBO) has been suggested to influ-
(Trautwein and McKay 2020). Lifestyle changes (e.g. dietary
ence the serum lipid profile. intervention) and medication are two crucial elements in the
 We reviewed the effects of RBO consumption on the
management of dyslipidemia. Changes in one’s diet can
lipid profile in adults. reduce the need for medications and decrease their side
 According to our findings, RBO consumption signifi- effects (Ghobadi, Hassanzadeh-Rostami, Mohammadian,
cantly decreases serum total cholesterol, low-density lipo- Zare, et al. 2019). In particular, oils, thanks to their compos-
protein cholesterol and triglyceride levels. ition, influence the hypercholesterolemia risk in a significant
 RBO had no significant effects on serum high-density manner. Due to their richness in various fatty acid and
lipoprotein cholesterol levels. exclusive ingredients, edible fats and oils can alter the lipid
profile (Ghobadi, Hassanzadeh-Rostami, Mohammadian,
Introduction Nikfetrat, et al. 2019). Recently, rice bran oil (RBO) has
been regarded as a nutraceutical/functional food. This edible
Abnormal lipid metabolism is a condition that acknowl- oil has been routinely consumed in several Asian countries,
edged as risk factor for life style related diseases. Lifestyle- namely Japan, Korea, China, Taiwan and Thailand, and has
related diseases, such as stroke, heart disease, and diabetes, also gained popularity on the Western markets due to its
are main examples of noncommunicable diseases and are potential nutritional importance and health benefits. The
now the major cause of death in the world (Aida et al. composition of RBO exhibits a good balance between unsat-
2020). Dyslipidemia is a metabolic abnormality leading to urated fatty acids (FA) (oleic and linoleic) and saturated FA
an increase in plasma total cholesterol (TC) and triglycerides (palmitic). In addition, RBO contains a great variety of bio-
(TG) levels. It is described by elevated low-density active phytochemicals with confirmed nutritional benefits,

CONTACT Farzad Shidfar [email protected] Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Teheran, Iran
#
Present address: Pediatric Gastroenterology, Hepatology and Nutrition Research Center, Research Institute for Children’s Health, Shahid Beheshti University of
Medical sciences, Tehran, Iran.
Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1895062.
ß 2021 Taylor & Francis Group, LLC
2 B. POURRAJAB ET AL.

e.g. c-oryzanol (a mixture of ferulic acid esters of triterpene Study selection and eligibility criteria
alcohols such as campesteryl ferulate, cycloartenyl ferulate
Two independent researchers (B.P. & S.F.) performed the
and 24-methylenecycloartanyl ferulate) and vitamin E ana-
screening of the titles and abstracts and the further assess-
logs, e.g. tocotrienols (a, ß, d and especially c-tocotrienol)
ment of the full-texts of the qualified articles. All the pub-
and tocopherols (d-tocopherol). What sets RBO apart from
lished controlled clinical trials (either with a parallel or a
other vegetable oils available on the market is that it is the
cross-over design) that reported the results of RBO con-
only source of c-oryzanol, which has been reported to have sumption on the serum lipids (TC, LDL-c, HDL-c or TG) in
an excellent nutritional functionality and is well-known to adults (subjects aged 18 years) were considered. A specific
reduce plasma cholesterol (Tong and Jinsong 2019, Fujiwara time frame was not considered for the search and we
2019). Research conducted on animal models and in reviewed all the studies conducted on this topic until
humans has concluded that RBO possesses considerable October 2020. The exclusion criteria were: 1) animal and
lipid-lowering effects. Noteworthy, experiments in which in vitro studies; 2) studies conducted on children, including
RBO or its unsaponifiable fractions (total tocopherols, c-ory- adolescents; 3) studies which examined the effect of RBO in
zanol, and squalene) were fed to animals have demonstrated combination with other oils; 4) studies that investigated rice
that the unsaponifiable fractions of RBO are efficient in low- bran, rice bran powder, rice bran fiber, and rice bran forti-
ering circulating lipids levels and the aortic accumulation of fied foods; 5) studies that examined only certain compounds
cholesterol esters (Rukmini and Raghuram 1991, Friedman of the RBO, such as c-oryzanol, vitamin E (a-, b-, c-, and
2013). However, studies conducted on human subjects have d-tocopherols and tocotrienols) or ferulic acid; 6) studies
produced contradictory results. To our knowledge, so far have examined RBO together with a specific dietary pattern;
only one meta-analysis has investigated the effects of RBO 7) studies comparing RBO with brown RBO; 8) studies that
consumption on the lipid profile in humans. The aforemen- examined rice bran extract that was not RBO; 9) studies that
tioned study, conducted by Jolfaie et al.(Jolfaie et al. 2016), evaluated margarine fortified with specific compounds or
provided contradicting results and was limited by several sterols in RBO; 10) studies comparing RBO with rice bran
flaws. Moreover, since it was conducted in 2015, data pub- powder; 11) studies in which the control group was another
lished from 2015 until now has not been evaluated. oil; 12) studies in which the duration of the intervention
Consequently, we decided to conduct a systematic review was <2 weeks; 13) studies without complete information or
and meta-analysis to study the effect of RBO consumption without a control group; 14) unrelated or inaccessible stud-
on the lipid profile in human adults. ies; 15) studies which evaluated other elements rather than
the lipid profile; 16) studies in which the results were
reported in the form of illegible graphs; 17) studies with
duplicate data found in another study; and 18) articles with
Methods other study designs except for a clinical trial design.
The current systematic review and meta-analysis was con-
ducted in agreement with the Preferred Reporting Items for Data extraction
Systematic Reviews and Meta-Analyses (PRISMA) guidelines
(Moher et al. 2015) in terms of processing, analyzing, and Two independent researchers (B.P.) and (M.H.S.) selected
the studies based on the inclusion and exclusion criteria.
reporting of the data.
Any discrepancy between the researchers was solved by con-
sulting with a third researcher (F.S.H.). The following infor-
mation was collected: author’s name, year of publication,
Search strategy study location, clinical trial design, study population, mean
age, sex, sample size, intervention group, control group,
The PubMed/Medline, Scopus, Clarivate Analytics’ Web of RBO dosage, control oil dosage, and duration of interven-
Science, Cochrane Central Register of Controlled Trials tion. This information is presented in Table 1.
(CENTRAL) and Google Scholar online databases were
searched until October 7th 2020 to find appropriate studies
published before this date, without language, time or any Quality assessment
other limitations. The type of article was restricted to The quality of the studies was independently assessed by 2
randomized controlled trials (RCTs) or clinical trials. We researchers (B.P.) and (F.S.H.) according to the Cochrane
used the following keywords: ((cholesterol) OR (LDL) OR Handbook for Systematic Reviews of Interventions, version
(TC) OR (HDL) OR (triglyceride) OR (TG) OR (lip- 5.1.0 (Higgins 2008) and by evaluating the following criteria:
oprotein) OR ("lipid profile") OR (Lipid) OR ("cardiovas- 1) random sequence generation, 2) allocation concealment,
cular disease") OR ("heart disease") OR 3) blinding of participants and personnel, 4) blinding of out-
(hypercholesterolemia)) AND ((rice oil) OR ("rice bran") come assessment, 5) incomplete outcome data, and 6) select-
OR ("rice bran oil") OR ("rice germ oil") OR ("rice bran ive outcome reporting. There were six key areas according
extract") OR ("oryza sativa oil") OR ("oryza sativa bran")) to which each study was rated in terms of the overall risk of
NOT ((rat) OR (mouse) OR (vitro) OR (animal)) bias: low-risk (low for all key areas), high-risk (high for one
Table 1. Characteristics of the randomized clinical trials that were included in the systematic review.
Sample
Size Rice bran oil Control oil duration of
Mean Age Case/ Intervention dosage dosage intervention
Author (year) study location Clinical Trial Design Population (year) Sex Control group Control group (geram/day) (geram/day) (week)
1 (Chen and Taiwan cross over clinical trial Healthy 24 Male 10/10 RBO soybean oil NR NR 2.5
Tsai 1995)
2 (Chen and Taiwan cross over clinical trial Healthy 24 Male 10/10 RBO olive oil NR NR 2.5
Tsai 1995)
3 (Chen and Taiwan cross over clinical trial Healthy 24 Male 10/10 RBO liquid lard NR NR 2.5
Tsai 1995)
4 (Eady New Zealand randomized, double- Hypercholesterolemic 51.5 Both sexes 39/39 RBOS SS 20 NR 4
et al. 2011) blind, cross-
over trial
5 (Eady New Zealand randomized, double- Hypercholesterolemic 52.8 Both sexes 36/36 RBO sunflower oil 47.6 27.6 4
et al. 2011) blind, cross-
over trial
6 (Kuriyan India Randomized cross- Hypercholesterolemic 50 Both sexes 14/14 RBO refined NR NR 13
et al. 2005) over clinical trial sunflower
oil
7 (Lai Taiwan randomized single Type 2 Diabetes 56.8 NR 17/18 RBO soybean oil 18 18 5
et al. 2011) blind placebo
comparison study
8 (Lichtenstein United States randomized, double- Hypercholesterolemic 61 Both sexes 15/15 RBO corn oil NR NR 4.5
et al. 1994) blind, cross-
over trial
9 (Lichtenstein United States randomized, double- Hypercholesterolemic 61 Both sexes 15/15 RBO Canola oil NR NR 4.5
et al. 1994) blind, cross-
over trial
10 (Lichtenstein United States randomized, double- Hypercholesterolemic 61 Both sexes 15/15 RBO olive oil NR NR 4.5
et al. 1994) blind, cross-
over trial
11 (Most United States randomized, double- Healthy 33.6 Both sexes 14/14 RBO oil blend NR NR 5
et al. 2005) blind, cross- composed
over trial of peanut
oil, olive oil,
corn oil,
canola oil,
palm
oil, butter
12 (Salar, Faghih, Iran single-center, Type 2 Diabetes 51 Female 25/23 RBO sunflower oil 30 30 8
and randomized,
Pishdad controlled, parallel-
2016) group trial
13 (Salar, Faghih, Iran single-center, Type 2 Diabetes 51.1 Female 25/24 RBO Canola oil 30 30 8
and randomized,
Pishdad controlled, parallel-
2016) group trial
14 (Wijayanthie, Indonesia randomized, single- Type 2 Diabetes 48.9 Both sexes 10/10 RBO virgin olive oil 13.8 13.8 4
Gunarti, blind, crossover
and clinical trial
Manikam
2019)
CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION

NR: not report, RBO: Rice Bran Oil, RBOS: Rice Bran Oil Spread, SS: standard sprea
3
4 B. POURRAJAB ET AL.

STATA version 11.0 was used for statistical analysis (Stata

Corp, College Station, TX) and we considered P-values
<0.05 statistically significant.

Results
Study selection
A flow chart describing the literature search and the selec-
tion is presented in Figure 1. Using the key terms of the
study, we identified 3160 articles through searching the data-
bases and three additional articles through other sources.
Firstly, duplicate articles (n ¼ 813) were removed and then
another 2319 articles, approved to be irrelevant, were
removed after reading their titles and abstracts. Next, we
assessed the full-texts of the remaining 31 articles of which
23 articles were excluded for the subsequent reasons: 1. only
the compounds in RBO have been investigated and not
RBO itself (n ¼ 7) (Berger et al. 2005b, Ishihara 1984,
Kerckhoffs et al. 2000, Qureshi et al. 1997, Vissers et al.
2000, Weststrate and Meijer 1998, Bumrungpert et al. 2019);
2. rice bran extract but not RBO has been studied (n ¼ 2)
(Ito, Nakashima, and Matsuoka 2015, Nhung et al. 2016); 3.
lack of a control group (n ¼ 1) (Rajnarayana, Prabhakar, and
Krishna 2001); 4. the control group was another compound
rather than an oil (n ¼ 4) (Calvo-Castro et al. 2019,
Figure 1. Flow chart of the study selection process. Kustiyah et al. 2019, Shakib, Gabrial, and Gabrial 2014,
Zavoshy, Mostafa, and Hassan 2012); 5. the study design
or more key area) and unclear risk (unclear for one or more was cross-sectional (n ¼ 1) (Maurya, Arya, and Sengar
key area). 2020); 6. rice bran or rice bran powder were examined
(n ¼ 2) (Murata et al. 2007, Sanders and Reddy 1992); 7. the
period of the study was <2 weeks (n ¼ 2) (Oshima, Suzuki,
Data synthesis and statistical analysis
and Imai 1972, Suzuki and Oshima 1970); 8. the study did
For all effects, the effect sizes were determined by the mean not report the baseline values and changes (n ¼ 1)
difference between the intervention and the control group at (Utarwuthipong et al. 2009); 9. the outcomes were reported
follow-up. Where the effect size was not stated, the differ- in the form of illegible graphs (n ¼ 1) (Tan et al. 2017); 11.
ence in the mean values at the baseline and at the end of the studies were inaccessible (n¼) (Raghuram, Brahmaji
the study were used. We elicited the mean and the standard Rao, and Rukmini 1989); and 12. the study data were
deviation (SD) from the reviewed studies and where the reported as a duplicate from another study (n ¼ 1) (Schwab
data were described in a different format. This technique et al. 1998). In the study by Bumrungpert
was used by Hozo et al. as follows: SD ¼ square root [(SD et al.(Bumrungpert et al. 2019), three different doses of
pretreatment) 2 þ (SD post-treatment) 2 – (2 R  SD c-oryzanol in RBO were compared with soybean oil. Since
pretreatment  SD post-treatment)] (Hozo, Djulbegovic, and most of the studies included in the present meta-analysis
Hozo 2005). The random effects model (DerSimonian and did not report the dose of c-oryzanol, it was not possible to
Laird method) was used in order to evaluate the effect sizes perform a subgroup analysis based on the c-oryzanol dosage
and the results were provided across weighted mean differ- and consequently this study was omitted. On the other
ence (WMD) and 95% confidence intervals (CI). We used hand, in research of Berger et al. (Berger et al. 2005b), pea-
the Plot digitizer software when the results only existed in nut oil was administered to patients for 2 weeks in the run-
the graphic form. Heterogeneity was calculated by the I2 in period and then two different doses of c-oryzanol were
index (Fatahi et al. 2018). We considered an I2 index greater compared to 4 weeks. Therefore, this study was also omitted.
than 50% as an index of significant heterogeneity among the Schwab et al.(Schwab et al. 1998) reported duplicate data
studies. Subgroup analysis was conducted to recognize fac- from the study of Lichtenstein et al. (Lichtenstein et al.
tors for high heterogeneity. We considered the values less or 1994) and since their only new report was the comparison
more than the median as the cutoff values for each above of RBO with beef tallow which is not a liquid oil (the type
mentioned quantitative parameter of subgroups. The sensi- and physical form of the beef tallow was not reported), it
tivity analysis was done by utilizing the leave-one-out was not entered into the analysis. The two reviewers (B.P.)
method to measure the impact of each study on the results. and (F.S.H.) approved the study screening procedure.
We used the funnel plot to determine publication bias by Although we finally selected eight articles for the analysis,
either Begg’s rank correlation or Eggers’ regression test. some of them can be viewed as separate trials because, in
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 5

these studies, RBO was compared to more than one type of run-in period was only mentioned in 4 studies (Chen and
oil (Salar, Faghih, and Pishdad 2016, Lichtenstein et al. Tsai 1995, Eady et al. 2011, Lichtenstein et al. 1994, Salar,
1994, Eady et al. 2011, Chen and Tsai 1995). Therefore, we Faghih, and Pishdad 2016). Participants did not take choles-
included eight articles in this systematic review with the terol-lowering medication in all the studies except for one
effect sizes of 14. (Lai et al. 2011) in which this aspect was not mentioned. In
none of the studies, the type of intervention was not differ-
ent in the intervention and control groups, except for the
Study and participant characteristics
oil consumed.
The characteristics of the studies included in the present sys-
tematic review and meta-analysis are displayed in Table 1.
Risk of bias assessment
Two studies were conducted in Taiwan (Chen and Tsai
1995, Lai et al. 2011), two in the United States (Most et al. As shown in Table 3, except for two studies (Eady et al.
2005, Lichtenstein et al. 1994) and the others were con- 2011, Salar, Faghih, and Pishdad 2016) that were considered
ducted in New Zealand, India, Iran and Indonesia. From the as having a low risk of bias in the random sequence gener-
total of 8 articles, two studies were parallel in design (Lai ation, the other studies did not explicitly mention the ran-
et al. 2011, Salar, Faghih, and Pishdad 2016) and the others domization or random sequence generation methods.
were cross-over in design. Three studies were double- Therefore, they were regarded as having an unclear risk of
blinded (Eady et al. 2011, Lichtenstein et al. 1994, Most bias. All the studies were assessed as having an unclear risk
et al. 2005) with 65 participants and two studies (Lai et al. of bias in the allocation concealment because they did not
2011, Wijayanthie, Gunarti, and Manikam 2019) with 45 mention the concealment or the method employed to per-
participants were single-blinded. The intervention duration form this operation. There were three studies (Eady et al.
was 2.5 weeks in one study (Chen and Tsai 1995), 4 weeks in 2011, Lichtenstein et al. 1994, Most et al. 2005) which were
two studies (Eady et al. 2011, Wijayanthie, Gunarti, and double-blind randomized controlled trials (RCTs) and were
Manikam 2019), 4.5 weeks in one study (Lichtenstein et al. thus considered as having a low risk of bias for the blinding
1994), 5 weeks in two studies (Lai et al. 2011, Most et al. of the participants and personnel. There were also two stud-
2005), 8 weeks in one study (Salar, Faghih, and Pishdad ies designed as single blind trials (Lai et al. 2011,
2016) and 13 weeks in one study (Kuriyan et al. 2005). Wijayanthie, Gunarti, and Manikam 2019) which were
Among these studies, two had examined the effects of RBO therefore considered as having an unclear risk of bias. None
in healthy subjects (Chen and Tsai 1995, Most et al. 2005), of the trials provided a clear explanation of the blinding of
three in hypercholesterolemic subjects (Eady et al. 2011, the outcome assessment and other issues. Three studies
Kuriyan et al. 2005, Lichtenstein et al. 1994) and three in (Lichtenstein et al. 1994, Most et al. 2005, Kuriyan et al.
patients with type 2 diabetes mellitus (Salar, Faghih, and 2005) were clear in providing incomplete outcome data and
Pishdad 2016, Wijayanthie, Gunarti, and Manikam 2019, Lai the other five articles were not clear on this matter. Three
et al. 2011). One study did not report the gender of the par- studies were assessed as having an unclear risk of bias in the
ticipants (Lai et al. 2011), five studies included both males selective reporting (Chen and Tsai 1995, Eady et al. 2011,
and females (Lichtenstein et al. 1994, Eady et al. 2011, Most et al. 2005), and the other five studies as having a low
Kuriyan et al. 2005, Wijayanthie, Gunarti, and Manikam risk of bias. Since all the studies were considered as having
2019, Most et al. 2005), one study only involved adult an unclear risk of bias for at least one of the six key
females (Salar, Faghih, and Pishdad 2016) and one was only domains, we found the quality of these studies “unclear”.
conducted on adult males (Chen and Tsai 1995). Overall,
the age range of the participants was 24-61 years. In 7 of the
14 effect sizes, the control group received oil containing a Meta-analysis
higher amount of MUFA than PUFA and SFA, i.e. olive oil A total of 14 studies with 270 participants (case ¼ 205, and
(Chen and Tsai 1995, Lichtenstein et al. 1994), virgin olive control ¼ 203) which reported TC, LDL-c, HDL-c and TG
oil (Wijayanthie, Gunarti, and Manikam 2019), liquid lard as outcome measures, were included in the meta-analysis
(Chen and Tsai 1995), canola oil (Lichtenstein et al. 1994, (Figure 2). Also, the results of subgroup analysis are shown
Salar, Faghih, and Pishdad 2016) and oil blend composed of in Table 2 and Supplementary Figures.
peanut oil, olive oil, corn oil, canola oil, palm oil and butter
(Most et al. 2005), while in the other 7 effect sizes, the con-
trol group received oil containing a higher amount of PUFA Total cholesterol (TC)
than MUFA and SFA, i.e. soybean oil (Chen and Tsai 1995, The combined results of the random-effects model displayed
Lai et al. 2011), sunflower oil (Eady et al. 2011, Kuriyan a significant decrease in TC following RBO consumption
et al. 2005, Salar, Faghih, and Pishdad 2016), corn oil (weight mean difference (WMD):
7.29 mg/dL, 95% CI:
(Lichtenstein et al. 1994) and standard oil spread (Eady
11.32,
3.25, P ¼ 0.000) without a significant heterogeneity
et al. 2011). In all the studies, the individual food and cal- among the studies (I2¼37.3%, P ¼ 0.078) (Figure 2a). The
orie intakes were checked, while 7 studies did not mention subgroup analysis for BMI showed that the reduction of TC
the use of a physical activity questionnaire, except for one was significantly higher in the overweight subjects (BMI: 25-
study which mentioned this issue (Kuriyan et al. 2005). The 29.9 kg/m2) (WMD¼
8.04; 95% CI:-14.45,
1.64)
6 B. POURRAJAB ET AL.

Figure 2. Forest plots from the meta-analysis of clinical trials investigating the effects of rice bran oil on (a) total cholesterol, (b) LDL-c, (c) HDL-c, and d) TG.

compared to those with a normal weight (BMI: 18-24.9 kg/ (Supplementary Figure 2b) and when the duration of the
m2) (Supplementary Figure 1a). In addition, the reduction intervention lasted  5 weeks (WMD¼
10.76; 95% CI:-
of TC was significantly higher in subjects  50 years old 17.78,
3.76) (Supplementary Figure 2c). The sensitivity
(WMD¼
8.72; 95% CI:-14.53,
2.92) (Supplementary analysis showed that no study had a significant effect on
Figure 1b) and when the duration of the intervention was the overall effect sizes of LDL-c (Supplementary Figure
 5 weeks (WMD¼
13.26; 95% CI:-21.77,
4.75) 5b), and the evaluation of the publication bias by the vis-
(Supplementary Figure 1c). Moreover, TC reduction was sig- ual inspection of the funnel plot did not show any evi-
nificant when the oils used contained a higher amount of dence of publication bias in the meta-analysis evaluating
MUFA versus (WMD¼
6.74; 95% CI:-10.87,
2.61) the effects of RBO on LDL-c (P ¼ 0.411) (Supplementary
(Supplementary Figure 1d). The sensitivity analysis indicated Figure 6b).
that no study had a significant impact on the overall effect
sizes of TC (Supplementary Figure 5a). The assessment of High-density lipoprotein cholesterol (HDL-c)
the publication bias by the visual inspection of the funnel The combined results of the random-effects model showed
plot did not show any evidence of publication bias in the no significant increase in HDL-c following RBO consump-
meta-analysis evaluating the effects of RBO on TC tion (WMD: 0.67 mg/dL, 95% CI:
0.86, 2.20, P ¼ 0.392)
(P ¼ 0.476) (Supplementary Figure 6a). and no significant heterogeneity among the studies
(I2¼6.4%, P ¼ 0.382) (Figure 2c). The sensitivity analysis
Low-density lipoprotein cholesterol (LDL-c) revealed that no study had a significant impact on the
The combined results of the random-effects model showed overall effect sizes of HDL-c (Supplementary Figure 5c).
a significant reduction in LDL-c following RBO consump- The assessment of the publication bias by the visual
tion (WMD:
7.62 mg/dL, 95% CI:
11.10,
4.14, inspection of the funnel plot did not display any evi-
dence of publication bias in the meta-analysis of RBO
P ¼ 0.000) without a significant heterogeneity among the
consumption on HDL-c (P ¼ 0.351) (Supplementary
studies (I2¼9.0%, P ¼ 0.354) (Figure 2b). The subgroup
Figure 6c).
analysis for BMI displayed that the reduction of LDL-c
was significantly higher in participants with a normal
weight (WMD¼
10.45; 95% CI:-18.30,
2.61) compared Triglycerides (TG)
to those diagnosed with overweight (WMD¼
5.84; 95% The combined results of the random-effects model showed a
CI:-10.53,
1.15) (Supplementary Figure 2a). In addition, significant reduction in TG following RBO consumption
the reduction in LDL-c was significantly higher in subjects (WMD:
9.19 mg/dL, 95% CI:
17.99,
0.38, P ¼ 0.041)
<50 years old (WMD¼
8.63; 95% CI:-15.18,
2.08) with relatively high heterogeneity among the studies
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 7

Table 2. Subgroup analyses for TC, LDL-c, HDL-c and TG based on BMI, age, duration of intervention and type of control (MUFA/PUFA rich oils).
Subgroups No. I2 (%) p-heterogeneity intergroup WMD(95% CI) P between
Total cholesterol 37.3 0.078
BMI 0.09
Normal 6 47.8 0.088
6.52 (-13.04, 0.00)
Overweight or obese 7 42.1 0.110
8.04 (-14.45,
1.64)
NR 1 – –
8.30 (-19.16, 2.56)
Age 0.35
< 50 years old 5 0.0 0.422
4.76 (-9.62, 0.10)
 50 years old 9 48.5 0.049
8.72 (-14.53,
2.92)
Duration of intervention 0.56
< 5 weeks 9 0.0 0.762
4.01 (-8.00,
0.03)
 5 weeks 5 62.7 0.030
13.26 (-21.77,
4.75)
Type of control (MUFA/PUFA rich oils) 0.69
PUFA 7 67.3 0.005
8.13 (-16.34, 0.09)
MUFA 7 0 0.885
6.74 (-10.87,
2.61)
LDL-c 9.0 0.354
BMI 0.61
Normal 6 49.7 0.077
10.45 (-18.30,
2.61)
Overweight or obese 7 0.0 0.771
5.84 (-10.53,
1.15)
NR 1 – –
9.10 (-17.69,
0.51)
Age 0.47
<50 years old 5 0.0 0.530
8.63 (-15.18,
2.08)
50 years old 9 27.1 0.203
7.34 (-11.91,
2.78)
Duration of intervention 0.59
< 5 weeks 9 0.0 0.777
5.62 (-10.18,
1.07)
 5 weeks 5 50.0 0.092
10.78 (-17.79,
3.76)
Type of control (MUFA/PUFA rich oils) 0.44
PUFA 7 40.6 0.121
7.86 (-13.71,
2.00)
MUFA 7 0.0 0.656
7.24 (-12.24,
2.23)
HDL-c 6.4 0.382
BMI 0.82
Normal 6 52.9 0.060 2.17 (-2.42, 6.75)
Overweight or obese 7 0.0 0.998
0.05 (-1.74, 1.63)
NR 1 – – 0.40 (-5.53, 6.33)
Age 0.48
<50 years old 5 49.7 0.094
0.52 (-6.36, 5.33)
50 years old 9 0.0 0.665 0.72 (-0.8, 2.25)
Duration of intervention 0.36
< 5 weeks 9 21.5 0.252 0.43 (-2.36, 3.23)
 5 weeks 5 0.0 0.449 0.64 (-1.12, 2.41)
Type of control (MUFA/PUFA rich oils) 0.67
PUFA 7 24.0 0.246 2.09 (-0.28, 4.47)
MUFA 7 0.0 0.773
0.67 (-2.78, 1.44)
TG 45.8 0.031
BMI 0.05
Normal 6 0.0 0.491
6.31 (-15.97, 3.35)
Overweight or obese 7 65.9 0.007
10.45 (-25.55, 4.66)
NR 1 – –
2.80 (-43.03, 37.43)
Age 0.06
<50 years old 5 0.0 0.860
5.13 (-15.37, 5.12)
50 years old 9 61.2 0.008
11.24 (-24.68, 2.19)
Duration of intervention 0.09
< 5 weeks 9 0.0 0.967
2.63 (-10.97, 5.70)
 5 weeks 5 68.4 0.013
20.52 (-38.98,
2.05)
Type of control (MUFA/PUFA rich oils) 0.04
PUFA 7 68.2 0.004
12.72 (-30.65, 5.22)
MUFA 7 0.0 0.827
7.14 (-15.22, 0.94)
WMD, weighted mean difference; BMI, body mass index; NR, no reported; PUFA, polyunsaturated fatty acid; MUFA, monounsaturated fatty acid; LDL-c, low dens-
ity lipoprotein-cholesterol; HDL-c, high density lipoprotein-cholesterol; TG, Triglyceride

(I2¼45.8%, P ¼ 0.031) (Figure 2d). BMI, age, duration of meta-analysis of the effect of RBO consumption on TG
intervention and type of control were considered as possible (P ¼ 0.324) (Supplementary Figure 6d).
sources of heterogeneity. The subgroup analysis indicated
that the reduction of TG was significantly higher if the dur-
ation of intervention was  5 weeks (WMD¼
20.52; 95% Discussion
CI:-38.98,
2.05) compared to <5 weeks (Supplementary
Figure 4c). The sensitivity analysis showed that no study This systematic review and meta-analysis evaluated eight
had a significant impact on the overall effect sizes of TG clinical controlled trials which had examined the effects of
(Supplementary Figure 5d), and the assessment of the publi- RBO on the serum lipid profiles in adults. The results of
cation bias by the visual inspection of the funnel plot did our analyzes showed that serum TC, LDL-c and TG levels
not demonstrate any evidence of publication bias in the significantly decreased in the group receiving RBO as
8 B. POURRAJAB ET AL.

Table 3. Risk of bias assessment according to the Cochrane collaboration’s risk of bias assessment tool.
Random Blinding of Blinding of Incomplete Overall
Study, Year sequence Allocation participants outcome outcome Selective assessment of
(reference) generation concealment and personnel assessment data reporting risk of bias
(Chen and Tsai 1995) Unclear Unclear Unclear Unclear Unclear Unclear Unclear
(Eady et al. 2011) Low Unclear Low Unclear Unclear Unclear Unclear
(Kuriyan et al. 2005) Unclear Unclear Unclear Unclear Low Low Unclear
(Lai et al. 2011) Unclear Unclear Unclear Unclear Unclear Low Unclear
(Lichtenstein et al. 1994) Unclear Unclear Low Unclear Low Low Unclear
(Most et al. 2005) Unclear Unclear Low Unclear Low Unclear Unclear
(Salar, Faghih, and Pishdad 2016) Low Unclear Unclear Unclear Unclear Low Unclear
(Wijayanthie, Gunarti, and Manikam 2019) Unclear Unclear Unclear Unclear Unclear Low Unclear

Table 4. Types of control oils based on their richness in fatty acids.

Oil Rich in SFA Rich in PUFA Rich in MUFA
Soybean oil 
Olive oil 
Virgin olive oil 
Canola oil 
Sunflower oil 
Corn oil 
Liquid lard 
Palm oil 
standard oil spread (SS) 
Oil blend composed of peanut oil, olive oil, corn oil,canola oil, palm oil, butter 

compared to the control group. However, the effect of RBO the control group and changes values, respectively. Finally,
on HDL-c was not statistically significant. Considering the since this study was conducted in 2015, it is certain that
association between RBO and serum TC, LDL-c, and HDL- related articles published after this date were not included in
c, our findings are similar to the previous meta-analysis that the meta-analysis. Therefore, these reasons might account
has been done in this area, but in the case of TG, the results for the observed differences in the results, namely the effect
are different. A previously conducted meta-analysis by of RBO on TG levels.
Jolfaie et al. (Jolfaie et al. 2016) has reported reductions in The fatty acid composition of RBO is very similar to pea-
TC (-12.65 mg/dL, 95% CI:
18.04,
7.27, P < 0.001) and nut oil, however peanut oil has little cholesterol-lowering
LDL-c (-6.91 mg/dL, 95% CI:
10.24,
3.57, P < 0.001) lev- effects as compared to RBO (Berger et al. 2005a, Trautwein
els after the consumption of RBO, but no significant effect and McKay 2020). Thus, the beneficial properties of RBO on
was observed on serum HDL-c (0.74 mg/dL, 95% CI:
0.57, TC and LDL-c are probably related to its richness in non-
2.05, P ¼ 0.27) and TG levels (-11.67 mg/dL, 95% CI: saponifiable compounds, namely sterols, c-oryzanol, and toco-

26.68, 3.33, P ¼ 0.127). Noteworthy, the aforementioned trienols. Lichtenstien et al. (Lichtenstein et al. 1994) showed
study is inconsistent for several reasons: 1. Different control that RBO has the highest concentration of b-sitosterol, cam-
groups were compared to RBO, meaning that both the oil pesterol and stigmasterol versus canola, olive or corn oil.
consumption control groups and the control groups that Sterols and cholesterol compete for absorption from the
were not given a specific oil and only had a low calorie diet mixed micelles in the gut due to their structural similarities
or weight maintenance diet, were analyzed together without (Moreau, Whitaker, and Hicks 2002). Considering their
any subgroup analysis in this regard, 2. The absence of sub- higher affinity for micelles (Armstrong and Carey 1987), plant
group analyses based on different oils that were included in sterols are responsible for a 30-40% decrease in the cholesterol
the meta-analysis as a control group, on their similarities, absorption (Ostlund 2007). On the other hand, c-oryzanol
e.g. the content in fatty acids, in order to understand better and tocotrienols in RBO decrease the rate of endogenous syn-
the effects of RBO on the lipid profile, 3. Two of the studies thesis of cholesterol by inhibiting the HMG-CoA reductase
that were included in the meta-analysis only examined spe- enzyme (Minhajuddin, Beg, and Iqbal 2005, Wang et al.
cific compounds in RBO, not RBO itself (Berger et al. 2015). Furthermore, the consumption of RBO increases the
2005b, Vissers et al. 2000), 4. One of the studies included in gene expression of cholesterol 7-alpha-hydroxylase (CYP7A1),
the meta-analysis (Lichtenstein et al. 1994) had more than which is the rate-limiting enzyme in the synthesis of bile acids
one effect size, due to the comparison of RBO with more from cholesterol. Therefore, a higher amount of cholesterol is
than one oil, and only one of these effect sizes were men- eliminated from the body in the form of bile acids. Moreover,
tioned in the meta-analysis, 5. A study dating back to 1995 RBO elevates the hepatic gene expression of the LDL-receptor,
and conducted by Chen et al. (Chen and Tsai 1995) was not resulting in an elevated cholesterol uptake from the blood
included in the meta-analysis, 6. The studies of into the liver (Chen and Cheng 2006). According to our
Rajanarayana et al. (Rajnarayana, Prabhakar, and Krishna results, RBO reduces TC in a higher extent when the control
2001) and Utarwuthipong et al. (Utarwuthipong et al. 2009), group consumed oils rich in MUFA versus PUFA. It seems
which were mentioned in the meta-analysis, did not report that, due to the cholesterol-lowering effects of PUFA
 CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION 9

(Abdelhamid et al. 2018, Hooper et al. 2015), the differences Conclusion

in TC between RBO consumption and high-PUFA oils con-
sumption are insignificant. Unexpectedly, the subgroup ana- The results of our meta-analysis show that RBO can signifi-
lysis results showed that the reduction of LDL-c was cantly decrease serum TC, LDL-c and TG levels in adults. In
significantly higher in participants with a normal weight com- addition, the results of the subgroup analysis for BMI
pared to those with overweight. A study by Kuryan et al. showed that the reduction of TC was significantly higher in
which was conducted on normal-weight hypercholesterolemic participants with overweight versus normal weight and in
patients has a major contribution to this finding. Since this subjects 50 years old, and also in comparison with oils rich
population had higher serum levels of LDL-c, the observed in MUFAs. However, in the case of LDL-c the reduction
effects of RBO were more significant. In addition, the impres- was higher in subjects <50 years old. Also, the reduction of
sive reduction of LDL-c in this trial may have been related to TC, LDL-c and TG was significantly higher when the dur-
the long duration of the intervention (13 weeks) (Kuriyan ation of the intervention was 5 weeks. Therefore, RBO
et al. 2005). consumption might be efficient in improving the lipid pro-
Previous animal and human studies have reported that file of adult subjects and thus prevent the development of
the prescription of RBO can reduce serum TG levels dyslipidemia/hyperlipidemia. However, for reliability and a
(Purushothama, Raina, and Hariharan 1995, Salar, Faghih, higher replicability of the results, future clinical trials, with
and Pishdad 2016). The omega-3 fatty acids content of RBO larger sample sizes, and different RBO doses are required in
can inhibit the apolipoprotein-B100 and VLDL-C synthesis order to elucidate the effect of RBO consumption on
and consequently cause a reduction in TG levels (Harris, serum lipids.
Dayspring, and Moran 2013, Lichtenstein et al. 1994). The
induction of the lipoprotein lipase by RBO is another sug-
gested mechanism responsible for the decrease in TG levels
Acknowledgments
(Salar, Faghih, and Pishdad 2016), however the exact mech- This meta-analysis was supported by the Iran University of Medical
anism remains unclear. Science, Tehran, Iran.
The present study has some strengths. Firstly, we applied
no time or language restrictions as inclusion criteria for the Conflict of interest
studies that evaluated the effects of RBO on the lipid profile.
Secondly, due to the fact that the oils employed as controls All authors have no conflicts of interest to declare.
differed in the studies, in order to reduce the bias related to
the inequality of the control groups, we divided the control
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