Received: 28 January 2019 | Revised: 17 April 2019 | Accepted: 21 April 2019

DOI: 10.1002/fsn3.1066

ORIGINAL RESEARCH

Unsalted tomato juice intake improves blood pressure and

serum low‐density lipoprotein cholesterol level in local
Japanese residents at risk of cardiovascular disease

Tamami Odai1 | Masakazu Terauchi2 | Daisaku Okamoto3 | Asuka Hirose1,2 |

Naoyuki Miyasaka1

1
Department of Obstetrics and
Gynecology, Tokyo Medical and Dental Abstract
University, Tokyo, Japan The aim of this study was to investigate the effects of unsalted tomato juice intake on
2
Department of Women’s Health, Tokyo
cardiovascular risk markers in local Japanese residents. Four hundred and eighty‐one
Medical and Dental University, Tokyo, Japan
3
Plant Breeding Institute Co., Ltd, Kuriyama,
local residents in Kuriyama, Japan, were enrolled in this study. Throughout the year
Yubari, Japan of the study, they were provided with as much unsalted tomato juice as they wanted.

Correspondence
Participants were screened for cardiovascular risk markers, such as blood pressure
Masakazu Terauchi, Department of (BP), serum lipid profile, and glucose tolerance, before and after the study period.
Women’s Health, Tokyo Medical and Dental
University, Tokyo, Japan.
Of the study participants, 260 participated in a detailed study of their lifestyle fac-
Email: [email protected] tors. The average ages of the 184 male and 297 female participants were 56.3 ± 13.3

Funding information
(mean ± SD) and 58.4 ± 11.7 years, respectively. BP in 94 participants with untreated
Kikkoman Corporation, Grant/Award prehypertension or hypertension was significantly lowered (systolic BP, 141.2 ± 12.1–
Number: x2136
137.0 ± 16.3 mmHg, p = 0.003; diastolic BP, 83.3 ± 10.1–80.9 ± 11.1 mmHg, p = 0.012,
paired t test). Further, the serum low‐density lipoprotein cholesterol (LDL‐C) level in
125 participants with untreated dyslipidemia significantly decreased (155.0 ± 23.2–
149.9 ± 25.0 mg/dl, p = 0.005, paired t test). These beneficial effects were not differ-
ent between sexes and among the different age groups. No significant difference in
lifestyle was found before and after the study. Unsalted tomato juice intake improved
systolic and diastolic BP and serum LDL‐C level in local Japanese residents at risk of
cardiovascular conditions.

KEYWORDS
cardiovascular diseases, hypertension, prehypertension, dyslipidemia, hypercholesterolemia

1 | I NTRO D U C TI O N en/). Even when CVDs are not fatal, they often result in permanent
damage to critical organs, which in turn causes activity restriction,
Cardiovascular diseases (CVDs) are the biggest causes of mortality nursing care, and reduced life expectancy. The main pathophysiolog-
worldwide, and according to the World Health Organization (WHO), ical cause of CVDs is atherosclerosis, which is a chronic inflammatory
they were responsible for 15.2 million global deaths (26.7%) in 2016 reaction that begins as a response to injury of the arterial intima (Ross,
(retrieved from http://www.who.int/media​centr​e/facts​heets/​fs310/​ 1999). This type of endothelial injury is induced by several factors, such

This is an open access article under the terms of the Creat​ive Commo​ns Attri​bution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.

Food Sci Nutr. 2019;7:2271–2279. 

www.foodscience-nutrition.com | 2271
2272 | ODAI et al.

as endotoxins, viruses, homocysteine, and cigarette smoke (Widlansky, TA B L E 1 The nutritional composition of the unsalted tomato
Gokce, Keaney, & Vita, 2003). Chronic endothelial injury in hyperten- juice used in the present study
sion, dyslipidemia, and diabetes are also important contributors of ath- Value per 200 ml
erosclerosis progression (National Heart, Lung, & Blood Institute, 2013 Nutrient (1 bottle)
retrieved from https​://www.nhlbi.nih.gov/health-topic​s/asses​sing-
Energy (kilocalories) 41
cardi​ovasc​ular-risk, Beckman, Creager, & Libby, 2002; Libby, Aikawa,
Protein (g) 2.2
& Schönbeck, 2000; Sander, Kukla, Klingelhöfer, Winbeck, & Conrad,
Fat (g) 0
2000). Therefore, it is crucial to regulate blood pressure (BP), and lipid
Sugars (g) 7.2
and glucose metabolism, to prevent the development of CVDs.
Dietary fiber (g) 1.8
Tomato contains a variety of bioactive compounds, such as carot-
enoid, vitamin A, calcium, and gamma‐aminobutyric acid, which may Sodium (mg) 16

play a role in maintaining physical and psychological health, including Calcium (mg) 23

the prevention of CVD (Hak et al., 2004; Yanai et al., 2017; Zorumski, Potassium (mg) 630
Paul, Izumi, Covey, & Mennerick, 2013). For example, the intake of Vitamin A (μg) 46
lycopene, a carotenoid rich in tomatoes and known to have strong GABA (mg) 99
antioxidant activity (Oshima, Ojima, Sakamoto, Ishiguro, & Terao, Lycopene (mg) 22
1996), has been reported to be inversely associated with the risk of 13‐oxo‐ODA (μg) 39.2
CVDs (Agarwal & Rao, 2000; Hak et al., 2004; Rissanen et al., 2001); Esculeoside A Unknown
the mechanism underlying this effect may be an improvement in the
serum lipid profile (Ried & Falker, 2011; Sesso, Wang, Ridker, & Buring,
2012; Yanai et al., 2017). There are also reports about the beneficial as possible. The participants received as much unsalted tomato
effects of lycopene on BP (Engelhard, Gazer, & Paran, 2006; Paran, juice (Nippon Del Monte) as they wanted throughout the year of the
Novack, Engelhard, & Hazan‐Halevy, 2009; Ried & Falker, 2011; Yanai study. The nutritional composition of the tomato juice used in the
et al., 2017). Esculeoside A, a saponin found in tomatoes, has also been present study, which was the same product as that was used in the
reported to suppress the activity of acyl‐CoA: cholesterol acyltransfer- previous study, is shown in Table 1 (Hirose et al., 2015). Participants
ase (ACAT), leading to an improvement in dyslipidemia (Nohara, 2010). kept records of daily tomato juice consumption, as well as any medi-
Furthermore, 13‐oxo‐9, 11‐octadecadienoic acid (13‐oxo‐ODA), a cal treatment and changes therein. We collected the participants’
conjugated linoleic acid newly identified in tomato juice, was shown to diaries every 3 months and calculated overall tomato juice con-
have antidyslipidemic effects (Kim et al., 2012). Recently, we reported sumption and total days of tomato juice intake throughout the study
that unsalted tomato juice intake for 8 weeks improved hypertriglycer- period based on the diaries, and then calculated the frequency of
idemia in middle‐aged Japanese women (Hirose et al., 2015), which tomato juice intake and the average tomato juice consumption per
prompted us to investigate the effects of tomato juice on cardiovas- day across the entire cohort. Five hundred and forty‐one residents,
cular risk markers, such as BP, and lipid and glucose metabolism, in who accounted for 4.3% of the population of Kuriyama, were en-
local Japanese male and female residents over a wider age range in rolled, and 481 (88.9%) completed this study (Figure 1).
this study. The study protocol was reviewed and approved by the Tokyo
Medical and Dental University Review Board, and written informed
consent was obtained from all participants. The study was con-
2 | M ATE R I A L S A N D M E TH O DS
ducted in accordance with the Declaration of Helsinki.

2.1 | Study population

2.2 | Measurement
The participants of the present study were recruited from among
the local residents in Kuriyama, Hokkaido, Japan. We sent flyers of The participants underwent an annual medical checkup, which was
this study to the local residents aged 20–74 years and held several conducted according to the public policy of the Japanese govern-
briefing sessions to the candidates to recruit as many participants ment to prevent lifestyle‐related diseases, before and after the study

FIGURE 1 Study flowchart

ODAI et al. | 2273

period. Physical examination was conducted by local government or sleeping, and smoking, were assessed with regard to possible lifestyle
medical institutions designated by the health insurance system ac- alterations.
cording to the protocol provided by the Japanese Ministry of Health,
Labor and Welfare. The medical examination included height, weight,
2.4 | Statistical analyses
abdominal circumference, systolic BP (SBP) and diastolic BP (DBP),
and serum levels of triglyceride (TG), high‐density lipoprotein cho- Statistical analyses were performed with GraphPad Prism version
lesterol (HDL‐C), low‐density lipoprotein cholesterol (LDL‐C), fasting 5.0 (GraphPad Software). Paired t test was used to compare the re-
plasma glucose (FPG), and hemoglobin A1c (HbA1c). Hypertension sults of physical and blood examination before and after the inter-
and impaired lipid and glucose metabolism were defined accord- vention, and differences between men and women were examined
ing to the diagnostic criteria in Japan. BP was categorized as nor- by unpaired t test. Changes in CVD risk markers among different age
mal (SBP <130 mmHg and DBP <85 mmHg), prehypertension (SBP, groups were compared with one‐way analysis of variance (ANOVA),
130–139 mmHg and/or DBP, 85–89 mmHg), and hypertension (SBP and changes in lifestyle were evaluated by chi‐square test. p values
≧140 mmHg and/or DBP ≧90 mmHg). Dyslipidemia was categorized <0.05 were considered statistically significant.
as hypertriglyceridemia (TG ≧150 mg/dl), hypo‐HDL cholesterolemia
(HDL <40 mg/dl), and hyper‐LDL cholesterolemia (LDL‐C ≧140 mg/
3 | R E S U LT S
dl). Participants who had FPG level ≧126 mg/dl and HbA1c ≧6.5%
were diagnosed with type 2 diabetes, and those with an FPG level
3.1 | Participants and tomato juice consumption
110–125 mg/dl and/or HbA1c 6.0%–6.4% were considered to have
impaired glucose tolerance. Four hundred and eighty‐one residents were enrolled, including 184
men and 297 women, aged 21–74 years. The average age (years) of
men and women was 56.3 ± 13.3 (mean ± SD) and 58.4 ± 11.7, re-
2.3 | Lifestyle factors
spectively. Among all participants, the frequency of daily unsalted
Of the 481 study participants, only 260 (54.1%) who underwent the tomato juice intake throughout the study period was 92.0 ± 12.2%,
medical checkup performed by the local government of Kuriyama and the average daily tomato juice consumption was 215 ± 84 ml.
participated in a detailed study of their lifestyle factors. This in- Most of the study participants consumed about 1 bottle (200 ml)
volved completing a questionnaire defined by the Japanese Ministry of unsalted tomato juice every day (Figure 2). Nine participants who
of Health, Labor and Welfare, before and after the intervention consumed <100 ml/day tomato juice were excluded from further
(Table 2). The questionnaire was composed of 22 questions, includ- analysis. Table 3 presents the overall results of physical and blood
ing past medical history, concurrent therapeutic agents, and lifestyle examination in 481 participants before and after the intervention. No
factors, such as diet, exercise, and smoking. Ten of these questions, significant differences were found in any factor before and after the
namely those about exercise, dietary habits, change in body weight, study period.

F I G U R E 2 Average daily tomato juice

consumption and cumulative frequency:
The number of participants for each
segment of daily tomato juice intake
(x‐axis) is represented in bars on the left‐
hand axis. The line and right‐hand axis
show the cumulative percentage
2274 | ODAI et al.

TA B L E 2 Questionnaire

No Questions

1–3 Are you currently taking the following medications?

a A drug to lower blood pressure
b Insulin injections or a drug to lower blood glucose
c A drug to lower cholesterol
4 Have you ever had stroke or have you ever received treatment for stroke?
5 Have you ever had heart disease or have you ever received treatment for heart disease?
6 Have you ever had chronic renal failure or have you ever received treatment for chronic renal failure (dialysis)?
7 Have you ever had anemia?
8 Are you a current regular smoker?
9 Have you gained 10 kg or more since you were 20 years old?
10 Have you been exercising at least 2 days per week, at 30 min each at an intensity that causes a slight sweat, for at least 1 year?
11 Do you walk for at least 1 hr every day or have equivalent physical activities in your daily life?
12 Do you walk faster than people of your age and sex?
13 Have you had a weight gain or loss of 3 kg or more over the last year?
14 How fast do you eat compared to others?
15 Do you have an evening meal within 2 hr before bedtime 3 days or more per week?
16 Do you eat after the evening meal 3 days or more per week?
17 Do you skip breakfast 3 days or more per week?
18 How often do you drink alcohol?
19 How much do you drink a day, in terms of glasses of refined sake?
20 Do you feel refreshed after a night's sleep?
21 Are you going to start or have you started lifestyle modifications?
22 Are you willing to get health counseling about lifestyle modifications if the opportunity arises?

Note: Defined by the Japanese Ministry of Health, Labor and Welfare.

94 participants with untreated prehypertension or hypertension

3.2 | Participants at risks of CVDs
included 43 men and 51 women aged 23–74 years, and the 127
Next, we compared BP before and after the study period in 94 participants with untreated dyslipidemia included 52 men and 73
participants with untreated prehypertension or hypertension. The women, ranging from 25 to 74 years. There were no significant
mean SBP and DBP were significantly lowered after a year of tomato differences in the mean changes in SBP, DBP, and serum LDL‐C
juice intake (SBP, 141.2 ± 12.1–137.0 ± 16.3 mmHg, p = 0.003; DBP, level between the sexes (SBP, −4.1 ± 15.0 and −4.3 ± 12.4 mmHg,
83.3 ± 10.1–80.9 ± 11.1 mmHg, p = 0.012, paired t test) (Figure 3a,b). p = 0.939; DBP, −1.52 ± 9.4 and −3.2 ± 8.6 mmHg, p = 0.362;
In 127 participants with untreated dyslipidemia, the mean serum TG LDL‐C, −4.8 ± 22.7 and −5.3 ± 18.0 mg/dl, p = 0.480, men and
and HDL‐C level did not change significantly after a year of tomato women, unpaired t test).
juice consumption (TG, 130.3 ± 69.6–136.8 ± 84.2 mg/dl, p = 0.255;
HDL‐C, 63.0 ± 17.3–61.6 ± 16.6 mg/dl, p = 0.051), whereas the
3.4 | Difference among age groups
mean serum LDL‐C level was significantly decreased (155.0 ± 23.2–
149.9 ± 25.0 mg/dl, p = 0.005, paired t test) (Figure 3c). We also eval- We also compared the changes in SBP, DBP, and the serum level of
uated glucose metabolism in 62 participants with untreated impaired LDL‐C before and after the intervention among different age groups.
glucose tolerance. No statistically significant change in FPG level The 94 participants with untreated prehypertension or hypertension
and HbA1c was observed after the study period (FPG, 107.8 ± 11.6– were divided into three age groups, namely young (23–54 years,
107.2 ± 11.7 mg/dl, p = 0.686; HbA1c, 6.1 ± 0.4–6.1 ± 0.4%, p = 0.385). n = 28), middle‐aged (55–64 years, n = 33), and old (65–74 years,
n = 33). No statistically significant differences in the mean changes
in SBP and DBP were observed among the groups (SBP: young,
3.3 | Difference between sexes
−0.2 ± 13.2; middle‐aged, −5.4 ± 15.1; old, −6.6 ± 11.7 mmHg;
Next, we compared the effects of unsalted tomato juice intake on p = 0.155, one‐way ANOVA, and DBP: young, −0.8 ± 9.4; middle‐
SBP, DBP, and serum LDL‐C level between men and women. The aged, −1.7 ± 9.6; old, −4.3 ± 7.8 mmHg; p = 0.281, respectively).
ODAI et al. | 2275

TA B L E 3 Results of physical and blood examination in 481

participants before and after the study period
3.5 | Change in lifestyle factors

Before the After the Finally, we investigated whether or not the improvements in car-
intervention intervention diovascular markers in participants at risk could be attributable to
changes in lifestyle during the study period. Among the 260 resi-
Mean SD Mean SD n
dents who participated in the detailed lifestyle study, 40 had un-
Body mass index, 23.3 3.5 23.4 3.5 481 treated prehypertension or hypertension, and 69 had untreated
kg/m2
dyslipidemia. The lifestyle factors did not differ significantly be-
Abdominal 81.5 9.5 81.3 9.6 469
tween the groups either before or after the study period (chi‐square
circumference, cm
test) (Table 4).
Systolic blood 125.1 17.3 124.9 16.8 480
pressure, mmHg
Diastolic blood 74.7 11.0 74.4 10.8 480
pressure, mmHg 4 | D I S CU S S I O N
Triglyceride, mg/dl 102.3 56.8 106.1 64.9 481
The present study showed that unsalted tomato juice intake may have
High‐density 65.3 16.8 65.4 16.4 481
lipoprotein choles- contribution to lower SBP and DBP in local Japanese residents who
terol, mg/dl had untreated prehypertension or hypertension, and improve serum
Low‐density 123.6 29.6 123.2 29.3 474 LDL‐C level in those who had untreated dyslipidemia. These ameliora-
lipoprotein tive effects were not different between sexes and different age groups
cholesterol, mg/dl
and could not be attributable to the alteration in lifestyle. To the best
Fasting plasma 95.8 16.6 95.3 13.8 430 of our knowledge, the current study is the first to investigate the ef-
glucose, mg/dl
fects of tomato or tomato product intake on CVD risk markers over
Hemoglobin A1c, % 5.6 0.5 5.7 0.5 407
the course of a year and over a wide age range.
Note: Data are presented as the mean and SD. There were no significant Tomatoes contain a variety of bioactive components that make
differences in any factor before and after the intervention. them and their products, including tomato juice, beneficial for health
(Engelhard et al., 2006; Hsu et al., 2008; Oshima et al., 1996; Paran
Dividing the 127 participants with untreated dyslipidemia into young et al., 2009; Ried & Falker, 2011; Sesso et al., 2012). Above all, ly-
(n = 39), middle‐aged (n = 43), and old (n = 43) in the same way, the copene is well known for its strong antioxidant activity and the
mean changes in serum LDL‐C level were not different significantly inhibition of LDL oxidation, which plays a key role in the initiation
among the groups (young, −5.0 ± 21.4; middle‐aged, −3.9 ± 18.6; old, and development of atherosclerosis. Several epidemiological stud-
−6.3 ± 20.5 mg/dl; p = 0.854, one‐way ANOVA). ies have suggested that lycopene could contribute to the prevention

F I G U R E 3 Systolic and diastolic blood

pressure, and the serum LDL‐C level
before and after the intervention: (a)
systolic and (b) diastolic blood pressure
in 94 participants with untreated
prehypertension or hypertension; (c) the
serum levels of LDL‐C in 125 participants
with untreated dyslipidemia. Data are
presented as the standard error of the
mean. *p < 0.05, ** < 0.01, versus before
the intervention, paired t test
2276 | ODAI et al.

TA B L E 4 Change in lifestyle factors

Untreated prehypertension or
hypertension Untreated dyslipidemia

Before (n) After (n) p value Before (n) After (n) p value

Exercise
Yes 8 32 0.439 18 13 0.415
No 12 28 51 56
Physical activity
Yes 17 23 1.000 25 32 0.300
No 16 24 44 37
Speed of walking
Fast 22 15 0.178 33 32 1.000
Normal 18 24 35 36
Speed of eating
Fast 14 14 1.000 20 18 0.706
Normal/Slow 26 26 48 51
Eating before
bedtime
Yes 2 4 0.675 9 7 0.791
No 38 36 60 62
Snack between
meals
Yes 4 5 1.000 8 4 0.366
No 36 35 61 65
Skip breakfast
Yes 1 2 1.000 4 7 0.532
No 39 38 64 62
Change in body
weight
Yes 6 6 1.000 14 15 1.000
No 33 34 55 54
Sleeping
Good 33 36 0.518 55 54 0.833
Bad 7 4 13 15
Smoking
Yes 7 4 1.000 13 15 0.833
No 33 36 55 54

Note: Data show the change of lifestyle factors in 40 participants with untreated prehyperten-
sion or hypertension and in 69 with untreated dyslipidemia before and after the study period. No
significant differences in lifestyle factors were found between the groups (chi‐square test).

of atherosclerosis and CVDs (Hak et al., 2004; Klipstein‐Grobusch Palozza, Simone, Catalano, Parrone, et al., 2011). The anti‐inflamma-
et al., 2000; Kohlmeier et al., 1997; Rissanen et al., 2003). For ex- tory effects of lycopene in the atherosclerosis process have also been
ample, the serum lycopene concentration was inversely associated shown (Palozza et al., 2010; Palozza, Simone, Catalano, Monego, et
with calcified deposits in the abdominal aorta (Klipstein‐Grobusch al., 2011). Studies suggested that lycopene could reduce the produc-
et al., 2000) and the intima‐media thickness of the common carotid tion of proinflammatory cytokines through activation of peroxisome
artery (Rissanen et al., 2003). Recently, novel molecular mechanisms proliferator‐activated receptor γ and inhibition of nuclear factor‐κB.
underlying lycopene's ability to prevent atherosclerosis have been Furthermore, the beneficial effects on BP (Engelhard et al., 2006;
identified: These include the regulation of cholesterol metabolism Palozza, Simone, Catalano, Monego, et al., 2011; Palozza, Simone,
by lycopene through the suppression of cholesterol synthesis and Catalano, Parrone, et al., 2011; Paran et al., 2009) and the amelio-
efflux in macrophages (Palozza, Parrone, Simone, & Catalano, 2010; rative effects of endothelial function by the antioxidant activity of
ODAI et al. | 2277

lycopene have been reported (Gajendragadkar et al., 2014; Kim, Paik, The present study has some limitations. Firstly, as most of the
et al., 2011; Zhu, Wang, & Xu, 2011). Although the mechanism is yet study participants consumed about one bottle of tomato juice
to be elucidated, our study showed the beneficial effects of unsalted (200 ml) every day, we could not evaluate whether the effects of
tomato juice intake on SBP, DBP, and LDL‐C; thus, our findings may tomato juice on CVD risk markers depended on the level of con-
support these reports of the beneficial properties of lycopene. sumption. Secondly, the detailed information of the diet each par-
Esculeoside A, a tomato saponin, has also been suggested to ticipant followed during the study period is lacking. We also did not
have protective effects on dyslipidemia and atherosclerosis de- assess the intake of other juices and nutritional supplements. Finally,
velopment by inhibiting ACAT (Fujiwara et al., 2007; Nohara, Ono, the study on lifestyle factors was conducted in only about half of
Ikeda, Fujiwara, & El‐Asar, 2010). Inhibition of ACAT decreases the the participants and the findings may not be applicable to the whole
absorption of diet‐derived cholesterol in the small intestine, macro- study population.
phage foam cell formation, and cholesterol synthesis in the liver. In In conclusion, our study shows that unsalted tomato juice in-
2007, Fujiwara et al. demonstrated that esculeoside A suppressed take could have improved systolic and diastolic blood pressure in
the activity of ACAT, reduced the serum levels of TG, LDL‐C, and Japanese residents who had untreated prehypertension or hyper-
total cholesterol, and improved atherosclerotic lesions in apolipo- tension, and also decreased the serum LDL‐C level in those who had
protein E‐deficient mice (Fujiwara et al., 2007). Esculeoside A could untreated dyslipidemia. As tomato juice is an affordable and readily
have played a role in improving serum LDL‐C level in our study par- product, it could be practical as applied a nutritional intervention to
ticipants although its amount in the tomato juice used in the current prevent CVDs in people at risk.
study was unknown.
Peroxisome proliferator‐activated receptors (PPARs), of which
AC K N OW L E D G M E N T S
three subtypes have been identified (α, β, γ), regulate energy ho-
meostasis, including lipid and glucose metabolism (Braissant, We appreciate the contribution of Ms. Mayumi Sogawa of the local
Foufelle, Scotto, Dauca, & Wahli, 1996; Varga, Czimmerer, & Nagy, government of Kuriyama in recruiting the study participants and col-
2011; Wahli, Braissant, & Desvergne, 1995). PPARα is strongly lecting the data. Authors are thankful to Kikkoman Corporation for
expressed in tissues with a high mitochondrial and peroxisomal financial support.
β‐oxidation activity, such as the heart, liver, kidney, and intestine
(Braissant et al., 1996), and activation of PPARα results in enhance-
C O N FL I C T O F I N T E R E S T
ment of fatty acid oxidation and improvement of dyslipidemia
(Wahli et al., 1995). Oxo‐octadecadienoic acid (oxo‐ODA) found in MT received an unrestricted research grant from Kikkoman
tomato was recently reported to act as a PPARα agonist ( Kim, Hirai, Corporation.
et al., 2011; Kim et al., 2012; Takahashi et al., 2011). Although four
structural isomers of oxo‐ODA were identified that activate PPARα
ETHICAL REVIEW
equally (Braissant et al., 1996; Kim et al., 2012), 9‐oxo‐10(E),12(E)‐
ODA and 13‐oxo‐ODA were the only ones detected in tomato This study was conducted in accordance with the Declaration of
juice (Takahashi et al., 2011). Kim et al. (2012) showed that 9‐ Helsinki. This study protocol was reviewed and approved by the
oxo‐10(E),12(E)‐ODA decreased cellular accumulation of TG in Tokyo Medical and Dental University Review Board.
mice hepatocytes, and 13‐oxo‐ODA reduced plasma and hepatic
TG level and plasma glucose level in obese diabetic mice. PPARα
I N FO R M E D C O N S E N T
activation also plays a role in antioxidant and anti‐inflammatory ef-
fects (Delerive, Gervois, Fruchart, & Staels, 2000; Deplanque et al., Written informed consent was obtained from all study participants.
2003; Ibarra‐Lara et al., 2010, 2012; Varga et al., 2011). It has been
suggested that PPARα stimulation induces antioxidant activity,
ORCID
leading to improvement in the activity of endothelial factors that
control blood pressure (Ibarra‐Lara et al., 2010) and cardiac func- Masakazu Terauchi https://orcid.org/0000-0001-5577-0094
tion (Ibarra‐Lara et al., 2012), and neuroprotective effects against
cerebral injury (Deplanque et al., 2003). Furthermore, the athero-
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