Asia Pac J Clin Nutr 2020;29(3):491-497

491

Original Article

Tomato juice preload has a significant impact on
postprandial glucose concentration in healthy women:
A randomized cross-over trial
Yuuki Saito RD1, Ayasa Nitta RD1, Saeko Imai PhD1, Shizuo Kajiyama MD2,3,
Takashi Miyawaki MD1, Neiko Ozasa MD4, Shintaro Kajiyama MD5,
Yoshitaka Hashimoto MD3, Michiaki Fukui MD3
1

Department of Food and Nutrition, Kyoto Women’s University, Kyoto, Japan
Kajiyama Clinic, Kyoto, Japan,
3
Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate Schoolof Medical Science, Kyoto, Japan,
4
Department of Cardiovascular Medicine, Kyoto University, Graduate School of Medicine, Kyoto, Japan,
5Japanese Red Cross Kyoto Second Hospital, Kyoto, Japan
2

Background and Objectives: Our aim was to evaluate the effect of consuming tomato juice before carbohydrateon postprandial glucose concentrations in healthy women. Methods and Study Design: In this randomized controlled cross-over study, 25 healthy women (age 21.6±3.8 years, HbA1c 5.3±0.2 %, mean±SD) consumed either
200 g of tomato juice, tomato, or water (control) at 30 min before consuming 200 g of boiled white rice at 9:00
and consumed identical lunch at 13:00 for 3 days. The blood glucose concentrations were measured by selfmonitoring blood glucose at 0, 30, 45, 60, 90, 150, and 210 min pre- and post-breakfast, and at 0, 30, 60, 120, 150,
and 180 min pre- and post-lunch. The concentration of postprandial glucose, incremental glucose peak (IGP), andincremental area under the curve for glucose after the test meals were compared among 3 days. Results: Incremental blood glucose concentrations at 60 min (2.32±0.16 vs 2.97±0.19 mmol/L, p<0.05, mean±SEM), 90 min(2.36±0.23 vs 3.23±0.24 mmol/L, p<0.01), and IGP (2.77±0.19 vs 3.68±0.22 mmol/L, p<0.001) in consuming
tomato juice 30 min before carbohydrate were all significantly lower than those of water, while IGP of consuming tomato was tended to be lower than that of water (2.82±0.19 mmolL, p=0.023). No significant difference wasobserved in glycaemic parameters after consuming lunch among 3 days. Conclusions: Consuming tomato juice
half hour before carbohydrate ameliorates the postprandial blood glucose concentrations, although total amountsof energy and carbohydrate of tomato juice are higher than those of water.

Key Words: diet, tomato juice, vegetable, postprandial glucose, carbohydrate, diabetes

INTRODUCTION
Postprandial hyperglycemia promotes arteriosclerosis inpeople with and without diabetes. Hyperglycemia causes
vascular endothelial disorders and inflammation, as aresults to develop arteriosclerosis, cerebral infarction, andmyocardial infarction.1 Thus, reducing the blood glucose
excursion is effective to decrease the risk of the macrovascular complications. Even for healthy individuals aswell as people with diabetes, suppressing postprandial
glucose concentration is one of the keys for extension ofhealthy life expectancy.
We have reported that a simple and easy meal plan of
consuming vegetables first and carbohydrates last was
effective to suppress the postprandial glucose concentrations and insulin secretion in people with and without
diabetes2-6 and this method is widely used for dietary education for patients with diabetes and healthy individuals
in Japan.7,8 A follow-up study of meal sequence was conducted and significant effects were confirmed on obese

type 2 diabetes patients in the United States.9
However, according to the National Health and Nutrition Survey in Japan, the average vegetable intake was276.5 g, which was below the target of 350 g that wasrecommended by Japanese Ministry of Health, Labor andWelfare.10 The Dietary Guidelines for Americans by theUnited States Department of Agriculture (USDA) recommended 2 and half cups of vegetable intake per day fora reference 2,000 kcal intake.11 Despite intensive public
educational campaigns, surveys showed that 70% of U.S.
people do not reach vegetable intake of the USDA recCorresponding Author: Prof. Saeko Imai, Department of Foodand Nutrition, Kyoto Women’s University, 35 Kitahiyoshi-cho,
Imakumano, Higashiyama-ku, Kyoto, 605-8501, Japan.
Tel: +81-75-531-7128; Fax: +81-75-531-7170
Email: imais@kyoto-wu.ac.jp; poooch@hotmail.co.jp
Manuscript received 07 April 2020. Initial review completed 12
April 2020. Revision accepted 27 April 2020.
doi: 10.6133/apjcn.202009_29(3).0007

492

Y Saito, A Nitta, S Imai, S Kajiyama, T Miyawaki, N Ozasa et alommendation, and surprisingly 25% of people do not eat
vegetable at all.12 There are several reasons for low vegetable intake, such as economic burden, lack of knowledgeof the benefits of vegetable intake, low availability offresh products, taste preference, and limited cooking timeand skills. Therefore eating vegetables every day is noteasy for many people.
A Mediterranean diet has been associated with broad
healthy benefits on human health13 and one of its signature food is tomato. Epidemiologic and intervention trials
of tomato juice have focused on serum lipids concentrations14,15 whereas the effect on postprandial blood glucose
has rarely been investigated. Tomato juice is easy to consume and lower cost than fresh vegetable, therefore it isimportant to approve if consuming tomato juice suppress
the postprandial blood glucose concentrations as well as
consuming vegetables. In this randomized controlled
cross-over study, we explored the effect of tomato juice
on postprandial glucose response after consuming breakfast. In addition, we explored the glycaemic response tolunch to clarify how long the effect of consuming tomato
juice continued in healthy individuals.
METHODS
Subject of study
We recruited volunteers as research participants in Kyoto
Women’s University (Supplemental Figure). Exclusion
criteria are as follows. (1) People with type 1 and type 2
diabetes (2) taking drugs that affect blood glucose concentrations (3) pregnant or willing to become pregnant (4)smoking more than 40 cigarettes per day or drinking 50
ml alcohol per day (5) people with mental illness (6) people who were considered inappropriate for the study by
the doctor. This study was conducted after complying
with the ethical guidelines for medical research involving
human subjects in accordance to the Helsinki Declaration.
The study was approval by the Clinical Research Review
Committee in Kyoto Women's University (30-5) and registered UMIN-CTR (000034944). The study purpose,design, and risks of the study were explained to each participant and the written informed consent was obtained
prior to the study. The study was conducted between Nov.
2018 and Oct. 2019.

Test meal
The composition and macronutrient content of the test
meals as breakfast were shown in Table 1. The nutritional
contents of the test meals were analyzed by computer
software (Microsoft Excel Eiyokun for Windows ver.7.0
Kenpakusya, Tokyo, Japan). Participants consumed either
200 g of tomato juice (Kagome Co., Ltd., Tokyo), 200 gof tomato, or 200 g of water (control) at 30 min before
consuming 200 g of boiled white rice with herb salt (0.7 gof salt, Mishima Foods Co., Ltd., Hiroshima, Japan) for 3
separate mornings (Figure 1). The amounts of nutrients intomato and tomato juice were adjusted to be equal, but
the amount of energy, carbohydrate content, and dietaryfiber in water (control) were less than tomato and tomato
juice (Table 1). All participants consumed identical lunchat 13:00 consisting of 100 g of tomato, 80 g of spinach,
200 g of boiled white rice, and the frozen lunch box offried fish and vegetable (Tokatsu Foods, Yokohama, Japan) with energy 624 kcal, protein 25.1 g, lipid 11.5 g,
carbohydrate 104.0 g, and dietary fiber 8.1 g for 3 days.
Study method
Three weeks prior to the study, the anthropometric measurements and blood samples of participants were examined in Rakuwakai Toji Minami Hospital. Fasting blood
glucose (FBG) was measured using amperometic methodand Haemoglobin A1c (HbA1c) were determined byhigh-performance liquid chromatography (HPLC) method.
This study is a randomized controlled three-treatment
cross-over within-participant clinical trial (Figure 1 andSupplemental Figure). The participants consumed 200 gof tomato juice, tomato, or water at 8:30 and 30 min later
consumed 200 g of boiled white rice and consumed lunchat 13:00 (Figure 1). All meals were prepared and servedby the research group on 3 days at Kyoto Women’s University. Each participant performed the capillary finger
pricks (Gentlet, Sanwa Chemical Institute, Nagoya, Japan)
and blood glucose analyses with self-monitoring blood
glucose (SMBG) device (Glutest neo alpha, Sanwa
Chemical Institute, Nagoya, Japan). The blood glucose
concentrations were measured at 0, 30, 45, 60, 90, 150,
and 210 min pre- and post-breakfast and at 0, 30, 60, 120,
150, and 180 min pre- and post-lunch (Figure 1). The

Table 1. Test meals of breakfast with tomato juice, tomato, and water (control) and macronutrient content of each
meal†
Boiled white rice (g)Tomato (g)Tomato juice (g)Energy (kcal)
Carbohydrate (g)Boiled white rice (g)Shiso seasoning (g)Tomato(g)Tomato juice (g)Dietary fiber (g)Fat (g)Protein (g)Salt (g)†Tomato juice
200
―
200
379
81.9
73.6
0.5
―
7.8
2.2
0.6
7.0
1.2

Tomato
200
200
―
377
81.5
73.6
0.5
7.4
―
2.8
0.8
6.6
0.7

Water (control)
200
―
―
339
74.1
73.6
0.5
―
―
0.8
0.6
5.2
0.7

The nutritional contents of the test meals were analyzed by computer software (Microsoft Excel Eiyokun for Windows ver.7.0
Kenpakusya, Tokyo, Japan).

Tomato juice preload has impact on blood glucose

493

Figure 1. The study protocol: all participants consumed 200 g of tomato juice, tomato, or water at 8:30 and 30 min later consumed 200 gof boiled white rice and consumed identical lunch with main dish, vegetable, and boiled white rice at 13:00. Each participant performed
the capillary finger pricks and blood analyses with self-monitoring blood glucose (SMBG) device. The blood glucose concentrations were
measured at 0, 30, 45, 60, 90, 150 and 210 min pre- and post-breakfast and at 0, 30, 60, 120, 150, and 180 min pre- and post-lunch.

incremental glucose concentrations, incremental glucose
peak (IGP), and incremental area under the curve for glucose (IAUC) after the test meals were compared among 3
days.
Data analysis
Sample size of 19 participants conferred a 90% power todetect a 5% difference (G*Power 3.1, Heinrich-HeineUniversität Düsseldorf, Germany) in incremental glucose
peak (IGP) based on our previous study of eating vegetable before carbohydrate in healthy individuals.3 Twenty
five participants were enrolled and completed the study.
Incremental blood glucose concentrations and IGP were
calculated by subtracting the blood glucose concentrationof baseline at 8:30 for breakfast and at 13:00 for lunch.
IAUC were calculated by trapezoidal method. As a normal distribution and homogeneity of all glycaemic pa-

rameters could not be confirmed by Shapiro-Wilk andLevene test, we performed a paired comparison by Wilcoxon matched-pairs signed-rank test followed by post
hoc Bonferroni’s inequality (p<0.017) when Friedman’s
test revealed significant effects for glycaemic parameters(p<0.05). All analyses were performed with SPSS Statistics version 22 software (IBM Corp., Armonk, NY, USA).
The data are reported as means ± standard error of themean (SEM) unless otherwise stated.
RESULTS
Twenty five healthy women (age 21.6±3.8 years, bodyweight 52.2±6.7 kg, BMI 21.0±1.8 kg/m2, FBG 4.9±0.29
mmol/L, HbA1c 5.3±0.2%: mean±SD) enrolled and completed the study. The incremental blood glucose concentrations were shown in Table. 2. When participants consumed tomato and tomato juice, the incremental blood

Table 2. Incremental blood glucose concentrations after consuming test meals with tomato juice, tomato, and water inhealthy women (n=25)

30 min after test meals (9:00)
45 min (9:15)
60 min (9:30)
90 min (10:00)
150 min (11:00)
210 min (12:00)
270 min (13:00)
30 min after lunch (13:30)
60 min (14:00)
120 min (15:00)
150 min (15:30)
180 min (16:00)

Tomato juice(mmol/L)
0.54±0.11†
0.81±0.10
2.32±0.16
2.36±0.23
1.41±0.15
0.74±0.17†
0.37±0.17
1.30±0.20
1.28±0.26
0.85±0.21
0.84±0.22
0.76±0.21

Tomato(mmol/L)
0.84±0.09
1.12±0.15
2.22±0.18
2.43±0.21
1.29±0.17
1.17±0.21
0.39±0.19
1.43±0.13
1.11±0.22
0.79±0.17
1.08±0.20
1.08±0.16

Water (control)(mmol/L)
0.09±0.07**##0.66±0.12
2.97±0.19*
3.23±0.24**
1.60±0.14
1.05±0.15
0.36±0.12
1.62±0.20
1.23±0.19
0.94±0.14
0.81±0.17
0.93±0.17

The incremental blood glucose concentrations were calculated each blood glucose concentration from the fasting value at 8:30.
Data are mean±SEM.
Tomato juice vs Water (control) *p<0.05, **p<0.01. Tomato vs Water (control) ##p<0.01. Tomato juice vs Tomato †p<0.05.

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Y Saito, A Nitta, S Imai, S Kajiyama, T Miyawaki, N Ozasa et al

glucose concentration at 9:00 were higher than that ofwater (control), however, after consuming boiled white
rice at 60 min (9:30) and 90 min (10:00), the incremental
blood glucose concentrations of tomato juice were significantly lower than those of water (Table 2). There was no
significant difference in incremental blood glucose concentrations between tomato juice and tomato, except incremental blood glucose concentration of tomato juice at
210 min (12:00) was significantly lower than that of tomato (p=0.015, Table 2). Moreover, IGP of tomato juice
was significantly lower than that of water (2.77±0.19 vs3.68±0.22 mmol/L, p<0.001, mean±SEM), and IGP of
tomato was tended to be lower than that of water(2.82±0.19 mmol/L, p=0.023, Figure 2A). However,
IAUC 8:30-11:00 of water showed no significant difference compared to those of tomato juice or tomato (water
270±15 vs tomato juice 228±18, vs tomato 236±16mmol/L×min, Figure 2B). No difference was observed inincremental blood glucose concentrations after consuming identical lunch at 13:00 among 3 days (Table 2).
DISCUSSION
In this acute cross-over trial, we showed that consuming
tomato juice 30 minutes prior to a carbohydrate meal was
effective to suppress the postprandial blood glucose concentrations compared to those of water in healthy women,
despite the energy and carbohydrate contents of water
were smaller than those of tomato or tomato juice. However, this acute effect of consuming tomato juice before
carbohydrate on amelioration of postprandial blood glucose concentration did not last more than 4 hours, since
there was no significant difference in glycaemic parameters after consuming lunch among 3 days. Interestingly,
IGP of lunch was lower than that of breakfast despite theamount of energy and carbohydrate of lunch were greaterthan those of breakfast. This phenomenon can be explained by the second meal effect that the insulin response is enhanced at the second meal as induced by the
first meal. In the present study the insulin release at lunch

might be enhanced by previous glucose exposure ofbreakfast. Additionally, Kameyama N et al reported thatthe combination of main dish and vegetable with boiled
rice was beneficial for lowering postprandial glucose
concentrations compared to boiled rice alone becausewith increased incretin response without excessive increased in insulin and GIP responses.16 Thus, this wasanother reason that the postprandial glucose concentrations after lunch with the combination of the main dish,vegetable, and boiled rice, showed the lower postprandial
glucose concentrations compared to those of breakfast in
the present study.
Our previous study of consuming vegetable before carbohydrate demonstrated 20-30% reduction of postprandial blood glucose concentration and insulin secretion compared to those of the reverse regimen of rice first in people with and without type 2 diabetes.2-4 Thus, in this study,
dietary fibers contain in tomato or tomato juice mightplay a role to suppress the postprandial blood glucose
concentrations. Because water-soluble dietary fiber has
stickiness to slow the absorption of carbohydrates anddelay the transition from the stomach to the small intestine, as a result, suppress the increase of postprandial glucose concentrations.17
Other beneficial acute effects of tomato juice havebeen demonstrated such as reducing of serum cholesterol
concentrations, triglyceride concentrations,14,18 inflammatory adipokine,19 and increasing the resting energy consumption.20 Chronic effects of tomato, lycopene, and carotenoid intake on lower prevalence of metabolic syndrome and cardiovascular risk factors have been reported,15,21 since high serum triglyceride concentration increases insulin resistance, reducing serum triglycerideconcentrations may lead to improve glycaemic control in
epidemiological research.22 Lycopene and 13-oxo-9, 11octadecadienoic acid (13-OXO-ODA) in tomato juice
have effect of antioxidant, modulating adipokine secretion, lowering plasma glucose and serum lipids concentrations in animal or cell culture.23,24 Therefore, tomato

Figure 2. IGP of breakfast (A) and IAUC 8:30-11:00 (B) in each test meal (n=25). Data are mean ± SEM. IGP; incremental glucose peak,
IAUC; incremental area under the curve for glucose. The IGP was calculated as the maximal blood glucose concentration from the fastingvalue at 8:30 over the 4-h postprandial period. The IAUC 8:30-11:00 for glucose was calculated by the trapezoidal method above the baseline value for glucose at 8:30. Tomato juice vs Water; ***p<0.001.

Tomato juice preload has impact on blood glucose

juice supplementation may be effective to shift circulating
adipokine concentrations for antiinflammtory profile andameliorate the postprandial glucose concentrations inhuman.
Similar report concluded the acute effect of vegetablejuice on suppression of the postprandial blood glucose
concentrations after consuming rice in healthy adults.25
However, the results of their study have problem to apply
for dietary education. Because they compared glycaemic
parameters between 150 g of boiled rice with water and
110 g of boiled rice with vegetable juice in order to unify
the amount of carbohydrate of test meals. Postprandial
glucose concentrations positively correlate the amount ofcarbohydrate, so postprandial blood glucose concentrations were lower in consuming 110g of boiled rice withvegetable juice than those in consuming 150 g of boiled
rice with water. Therefore, their conclusion of the acuteeffect of vegetable juice preload on amelioration of postprandial blood glucose concentrations is uncertain whether the effect is caused by vegetable juice preload or by thesmaller amount of boiled rice.
This study has two limitations that must be considered.
The first limitation of this study was that we measured
blood glucose concentration by SMBG, not by laboratory
analysis with venous sampling blood and did not measurehormone secretion. In our previous study, insulin secretion was suppressed 30% by consuming vegetable salad
before rice compared to the reverse regimen.2 Additionally Nishino K et al reported that the insulin secretion was
suppressed when the participants consumed the meal sequence of vegetables → meat→ rice.26 Consequently, inthis study, consuming tomato and tomato juice prior tocarbohydrate insulin secretion was presumed to be suppressed compared to that of consuming water. The second
limitation was that the study was conducted in Japanese
healthy women, the effect of different gender, people
with diabetes or impaired glucose tolerance has not been
confirmed. Care should be taken in extrapolating the present finding to other populations. However, in our seriesof studies on meal sequence and meal timing, the same
effects on postprandial glucose concentrations were obtained in patients with type 2 diabetes as well as healthypeople.2-6,27-30 Furthermore, it is not realistic to drink tomato juice a half hour prior to a carbohydrate meal indaily life, so it is necessary to verify the effect of suppress
the postprandial glucose concentrations by consuming
tomato juice less than 30 time before carbohydrate. Further studies are required for detailed mechanisms of tomato juice preload of carbohydrate on glycaemic responses in other population.
Conclusion
Consuming tomato juice 30 min before carbohydratemeal significantly reduce the postprandial glucose concentrations as well as tomato preload in healthy women,
although total amounts of energy and carbohydrate of
tomato juice and tomato were higher than those of water.
Tomato juice preload may be one of the convenient andcost effective methods to lower the postprandial glucose
concentrations.

495

ACKNOWLEDGEMENTS
We thank all of the investigators and volunteers who participated in this study.
AUTHOR DISCLOSURES
MF has received grants, honoraria and research supports from
AstraZeneca plc., Astellas Pharma Inc., Nippon Boehringer
Ingelheim Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan
K.K., Kyowa Hakko Kirin Company Ltd., Kissei Pharmaceutical Co., Ltd., MSD K.K., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Pharma Ltd., Sanwa Kagaku Kenkyusho
Co., Ltd., Sanofi K.K., Ono Pharmaceutical Co., Ltd., andTakeda Pharmaceutical Co., Ltd. The sponsors were not involved in the study design; in the collection, analysis, interpretation of data; in the writing of this manuscript; or in the decision
to submit the article for publication. The authors, their immediate families, and any research foundations with which they areaffiliated have not received any financial payments or otherbenefits from any commercial entity related to the subject of thisarticle. The authors declare that although they are affiliated witha department that is supported financially by a pharmaceuticalcompany, the authors received no current funding for this study
and this does not alter their adherence to all the journal policies
on sharing data and materials. The other authors have nothing todisclose.
This study was supported grant from Kyoto Women’s University.
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Tomato juice preload has impact on blood glucose

Supplemental figure 1. Flow diagram of the participants.

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