Asia Pac J Clin Nutr 2017;26(1):65-71

65

Original Article

The effects of tomato juice on male infertility
Yu Yamamoto MSc1, Koichi Aizawa PhD1, Makiko Mieno PhD2, Mika Karamatsu BSc3,
Yasuko Hirano MSc4, Kuniko Furui MSc4, Tatsuya Miyashita MSc1,
Kazumitsu Yamazaki MD5, Takahiro Inakuma PhD1,6, Ikuo Sato MD, PhD7,
Hiroyuki Suganuma PhD1, Teruaki Iwamoto MD, PhD3
1

Research and Development Division, Kagome, Nasushiobara, Japan
Center for Information, Jichi Medical University, Shimotsuke, Japan
3
Center for Infertility and IVF, International University of Health and Welfare Hospital, Nasushiobara,
Japan
4
Department of Pharmacy, International University of Health and Welfare Hospital, Nasushiobara, Japan
5
Department of Urology, International University of Health and Welfare Hospital, Nasushiobara, Japan
6
Department of Food and Nutrition, Facility of Contemporary Human Life Science, Tezukayama University,Japan
7
Department of Obstetrics and Gynecology, International University of Health and Welfare Hospital,
Nasushiobara, Japan
2

Background and Objectives: This study aimed to investigate the effects of tomato juice consumption on seminal plasma lycopene levels and sperm parameters in infertile men. Methods and Study Design: Subjects weremale infertility patients with poor sperm concentration (<20×106/mL) and/or motility (<50%). Following a fourweek observation period, subjects were randomly assigned among three groups: a tomato juice group, an antioxidant group, and a control group. The subjects in the tomato juice group and the antioxidant group daily consumed
one can of tomato juice (containing 30 mg of lycopene) or one antioxidant capsule (containing vitamin C 600 mg,
vitamin E 200 mg, and glutathione 300 mg), respectively, for 12 weeks (feeding period). Seminal plasma lycopene levels and sperm parameters were measured every 6 weeks during the feeding period. Results: Forty-four
patients completed the study (control group: 12, antioxidant group: 15, tomato juice group: 17). In the tomato
juice group, plasma lycopene level was significantly increased at the 12th week of the feeding period. Moreover, adecrease in seminal plasma white blood cells and an increase in sperm motility in the tomato juice group were
statistically significant at the 12th and 6th weeks, respectively, compared to the control group. In the antioxidant
capsule group, no significant improvement was observed in semen parameters. Conclusions: In conclusion, regular consumption of tomato juice seems to improve sperm motility in infertile patients. This is the first report toshow that commercially available food, such as tomato juice, might be beneficial for male infertility.

Key Words: tomato, lycopene, male infertility, oxidative stress, sperm parameters

INTRODUCTION
Worldwide, 13-15% of couples are infertile,1 defined as
the inability to achieve pregnancy within 12 months ofregular sexual intercourse for couples. These infertile
couples seek medical treatment to improve their chancesof fertility and successful pregnancy. Male factors account for 25-50% of causes.2,3 About 60% of male infertility may be due to a genetic factor, with environmental
and host factors accounting for the rest. Many environmental and host factors are known, including industrial
chemicals, hormonal imbalances, alcohol consumption,and smoking.4 However, the reason these factors cause
male infertility has not been fully clarified. A recent report identified oxidative stress as a likely cause.5 Many
environmental and host factors may cause oxidative stressthrough excessive generation of reactive oxygen species(ROS); these damage spermatozoa by oxidizing cell
membranes, which contain large amounts of unsaturated

fatty acids. Lipid peroxidation of spermatozoa leads to aloss of membrane integrity and an increase in permeability, inactivation of cellular enzymes, and cell apoptosis.
The consequence is reduced sperm count and activity,
decreased motility, and abnormal morphology.6,7 Therefore, enhancement of antioxidant capacity to protect
spermatozoa from oxidative stresses could present a major opportunity for improving male infertility.8-10 Many
clinical studies have been performed on the possible
Corresponding Author: Yu Yamamoto, Research and Development Division, Kagome, 17 Nishitomiyama, Nasushiobarashi,
Tochigi, 329-2762, Japan.
Tel: +81-287-36-2935; Fax: +81-287-39-1038
Email: Yu_Yamamoto@kagome.co.jp
Manuscript received 02 July 2015. Initial review completed 04
August 2015. Revision accepted 09 September 2015.
doi: 10.6133/apjcn.102015.17

66

Y Yamamoto, K Aizawa, M Mieno, M Karamatsu, Y Hirano, K Furui, T Miyashita, K Yamazaki, T Inakuma and I Satobeneficial effects of treatment with antioxidants on maleinfertility.5
Lycopene is a red pigment found in fruits and vegetables, including tomatoes, watermelon, and apricots, and isreportedly one of the most efficient singlet oxygen
quenchers and peroxyl radical scavengers.11 Moreover,there are many reports that lycopene has a beneficial rolein prevention of chronic diseases, such as cardiovasculardisease, atherosclerosis, cancer, and neurodegenerative
disorders.12 Humans cannot synthesize lycopene, andmust consume vegetables and fruits that contain it.13 Lycopene absorbed from the intestine is carried by thebloodstream in lipoprotein particles, and is distributed tovarious tissues.
Lycopene is reportedly highly concentrated in the maletestis.14 Therefore, lycopene was expected to improve
male infertility by enhancing antioxidant capacity ofsperm, prompting a few clinical trials. Gupta reported thatadministration of lycopene (2 mg twice a day for 3
months) improved many semen parameters in men with
idiopathic nonobstructive oligo/astheno/teratozoospermia.
15
However, this is insufficient to conclude that lycopene
is beneficial for male infertility. Furthermore, there is noreport evaluating the effect of consumption of foods containing lycopene. Accordingly, we conducted an intervention study to clarify the beneficial effects of tomato juice,
which is rich in lycopene, on male fertility.

cording to WHO criteria 1999.16 The candidates wereinterviewed by a doctor, and those who smoked, had atomato allergy, or had a history of relevant illness, suchas adult-onset mumps orchitis, undescended testicles, or ahigh semen white blood cell (WBC) count (≥1×106/mL)
were excluded. Consequently, 54 subjects aged 26-50(average: 36.9) participated in the experiment.

MATERIALS AND METHODS
Study design
We conducted a parallel group study with the approval of
the Ethics Committees of the International University of
Health and Welfare (IUHW) Hospital, and Kagome Co.,
Ltd. Following a four-week observation period, subjects
were assigned by the Department of Pharmacy, IUHW
Hospital, among three groups: a tomato juice group(n=21), an antioxidant group (n=17), and a control group(n=16). The subjects in the tomato juice group and theantioxidant group daily consumed one can of tomato juice
or one capsule of an antioxidant pill, respectively, for 12
weeks (feeding period). The subjects in the control groupwere not administered any experimental foods, and wererequired to avoid lycopene-rich foods containing tomatoes through the experimental period. Semen samples
were collected at 0, 6, and 12 weeks, and blood samples
were drawn at 0 and 12 weeks of the feeding period.

Semen samples and parameters
The participants provided semen samples by masturbation
in a room close to the laboratory. In the laboratory, thesamples were kept at 37°C until analyzed. The men had
been asked to abstain from ejaculation for at least 48
hours prior to participation in the study. The actual abstinence period was calculated as the time between the current and previous ejaculation, based on self-reported information. Semen volume was assessed by aspirating theentire sample into a graduated 5 mL syringe (Terumo,
Tokyo, Japan), after it was liquefied at 37°C. Sperm concentration, motility, and parameters of sperm movement(VCL = curvilinear velocity, μm/s; VSL = straight-line
velocity, μm/s; ALH = amplitude of lateral head displacement, μm; and STR = straightness and sperm head
pitch, μm) were evaluated by computer-assisted semen
analysis (CASA) (Hamilton Thorne Ceros, USA), using asperm motility analyzer system (SMAS) (Kashimura,
Japan). For the assessment of sperm concentration, thesamples were diluted in a FertiCult Flushing medium
without insulin (FertiPro, Belgium). A 10 μm-deep
Makler counting chamber (Oriental Instruments Co., Japan) was used for measurements of semen by CASA.
Smears were prepared for morphological evaluation andstained (Diff-Quick; Sysmex, Japan), and 200 cells were
finally assessed according to strict criteria,17 yielding thetotal abnormal rate. The number of leukocytes was assessed using Bürker-Türk hemocytometers (Kayagakilrikakogyo, Japan). The rest of the seminal plasma samples
were stored at -80°C until the levels of lycopene andmalondialdehyde (MDA) were quantified.

Experimental foods
A commercially available tomato juice (“Natsushibori”;
Kagome Co., Ltd., Japan) containing 30 mg of lycopene,
38 mg of vitamin C, and 3 mg of vitamin E in one can(190 g) was used as the experimental food for the tomato
juice group. The capsules for the antioxidant group contained vitamin C (CINAL Combination Tablet 600
mg/day, Shionogi Pharmaceutical Co., Japan), vitamin E(Juvela N Soft Capsule 200 mg/day, Tanabe Seiyaku
Hanbai Co., Japan), and glutathione (Tathion Tablet 300
mg/day, Eisai Co., Japan).
Subjects
We recruited male infertility patients with poor sperm
concentration (<20×106/mL) and/or motility (<50%) ac-

Plasma samples
A morning blood sample was drawn from the antecubital
vein for each patient, to reduce the effect of diurnal variation in hormone levels, and the serum was sent to the laboratory at the IUHW Hospital. Blood samples drawn
into a test tube containing disodium ethylenediaminetetraacetic acid (EDTA) were centrifuged at 1,087 g for 20
minutes, and the plasma samples were stored at -80°C
until levels of baseline characteristics (testosterone, follicle-stimulating hormone [FSH], luteinizing hormone[LH]),) and lycopene were quantified.
Baseline characteristics of plasma
Levels of testosterone were measured by an electrochemiluminescence immunoassay using Testosterone II (SRL,
Japan). Levels of FSH and LH were determined using atime-resolved immunofluorometric assay (SRL, Japan).
Measurements of these three hormones were carried out
by SRL, Inc.

Plasma and seminal plasma lycopene
Plasma and seminal plasma lycopene concentrations wereTomato juice and male infertility

determined by high performance liquid chromatography(HPLC). The plasma sample (200 μL) or seminal plasma
sample (500 μL) was withdrawn, and 1.0 mL of an ethanol solution of trans-β-8’-apocarotenal was added to theplasma as an internal standard. A solution of n-hexaneand dichloromethane (4:1, v/v, 5.0 mL) was added to the
mixture and centrifuged (1,087 g, 10 minutes). The supernatant (4.0 mL) was evaporated under nitrogen gas.
The residue was dissolved in 200 μL of solvent mixture(hexane/acetone/ethanol/toluene, 10:7:6:7, v/v/v/v), filtered with a 0.20 μm filter, and HPLC analysis was performed, using a photodiode array detector (SPD-M10,
Shimadzu, Japan) at a detecting wavelength of 472 nm,
and a C30 carotenoid column (250×4.6 mm, 5 μm; YMC,
Wilmington, NC, USA).
Physical examination
Physical examination of the infertile men was performed
by a urologist (TI). Testis disposition and varicoceles
were evaluated with the infertile subject standing. For
assessment, the same type of punched-out orchiometer
was used.18
Seminal plasma MDA
MDA concentration was spectrophotometrically determined using OxiSelect TBARS assay kit (Cell Biolabs,
San Diego, CA, USA).
Statistical analysis
Statistical analyses were performed using SPSS PC (version 5.0) software. Tukey’s test for multiple comparisons67

was employed as a post-hoc ANOVA for lycopene and
MDA levels compared to baseline. Dunnett’s test for multiple comparisons was employed as a post-hoc ANOVA
for comparing semen parameters between control and test
substance groups. Semen parameters were normalized bycube root transformation before analysis to correct for theskewed distribution.
RESULTS
Table 1 shows baseline characteristics of the study subjects. These were similar among all three groups, with nosignificant difference. A total of 54 patients were recruited, but only 44 completed the entire study (12/16, control
group; 15/17, antioxidant group; 17/21, tomato juicegroup). The reason for dropout was loss of follow-up in 8
(2 in the control group, 2 in the antioxidant group, and 4
in the tomato juice group), and successful fertilization
with a partner in 2 (2 in the control group).
Figure 1 shows mean values and ranges of plasma andseminal plasma lycopene levels during the experimental
period. Regular consumption of tomato juice for 12
weeks significantly increased the plasma lycopene level(p=0.017). The lycopene level in seminal plasma was
about one two-hundredth of that in blood plasma. Seminal
plasma lycopene levels were also increased at the 12th
week in the tomato juice group (p=0.023). There was asignificant correlation between blood plasma and seminal
plasma lycopene level (r=0.36, p=0.024).
Figure 2 describes the mean values and ranges of seminal plasma MDA. Sample measurement was incomplete(control group: 4, antioxidant group: 8, tomato juice

Table 1. Baseline characteristics of study patients in the three groups
Age (years)
Duration of infertility (years)
Rt. testis volume (mL)
Lt. testis volume (mL)
FSH (mIU/mL)
LH (mIU/mL)
Testosterone (ng/mL)

Control group36.2±1.91
2.34±0.70
19.5±1.01
18.8±1.10
5.35±0.99
2.75±0.33
5.49±0.58

Antioxidant group36.1±0.86
3.20±0.42
19.4±1.1818.9±1.20
6.01±1.19
2.56±0.22
4.96±0.35

Tomato juice group38.1±1.76
2.92±0.42
20.0±1.02
20.4±0.73
5.64±1.27
2.82±0.49
5.34±0.52

FSH: follicle-stimulating hormone; LH: luteinizing hormone.
Data are presented as mean ± standard error of the mean (SEM).

Figure 1. Mean lycopene levels in plasma (left) and seminal plasma (right) in the three groups. Data are presented as mean±SEM.
*
p<0.05 vs 0th week68

Y Yamamoto, K Aizawa, M Mieno, M Karamatsu, Y Hirano, K Furui, T Miyashita, K Yamazaki, T Inakuma and I Sato

Table 2. Changes in semen parameters in the three groups
Semen parameter
Semen volume (mL)
Sperm concentration (×106/mL)
Sperm motility (%)
Abnormal sperm rate (%)
Semen plasma WBC (×106/mL)
Straight-line velocity (μm/s)
Survilinear velocity (μm/s)
Straightness (%)
Amplitude of lateral head displacement (Hz)Sperm head pitch (μm)
Degree of sperm-nucleus damage (%)

0th week
3.70±0.57
51.5±7.6231.2±3.33
77.4±1.59
0.68±0.1223.7±1.39
55.8±4.25
44.1±1.25
0.39±0.06
10.1±0.59
27.2±3.60

Control group
6th week
4.19±0.67
65.5±22.5
27.7±4.66
78.3±2.30
0.73±0.18
22.9±2.73
56.4±5.73
38.3±2.98
0.49±0.13
9.11±0.82
37.5±5.83

12th week
4.10±0.47
38.4±8.87
30.3±6.35
81.6±1.39
0.65±0.19
21.8±1.40
54.0±4.18
42.0±2.26
0.34±0.07
12.2±1.1231.3±5.00

0th week
3.73±0.40
55.6±9.46
28.6±3.1283.8±1.41
0.65±0.14
24.4±1.47
58.1±3.40
42.0±2.17
0.40±0.06
10.4±0.23
20.3±2.21

Antioxidant group
6th week
12th week
3.72±0.47
3.25±0.39
61.0±13.543.6±6.72
26.3±4.37
33.8±4.97
81.1±2.30
81.4±2.03
0.68±0.26
0.62±0.10
25.0±2.91
23.4±2.18
61.0±5.1355.3±5.23
41.1±2.27
40.4±3.47
0.49±0.09
0.34±0.04
10.6±0.54
9.55±0.74
23.0±3.10
21.2±4.00

0th week
3.70±0.33
49.4±7.30
29.5±2.94
80.7±1.40
0.65±0.09
21.1±0.80
51.5±2.03
42.2±1.23
0.29±0.03
10.9±0.61
27.2±2.49

Tomato juice group
6th week
12th week
3.56±0.34
3.49±0.35
65.3±10.8
50.0±8.34
35.4±3.69
31.2±3.47
81.5±1.59
81.7± 0.15
0.63±0.17
0.44±0.06
21.7±1.39
22.7±1.20
54.2±3.07
54.6±2.54
40.1±1.02
42.6±1.28
0.36±0.04
0.74±0.38
10.0±0.46
10.1±0.53
27.5±3.03
26.9±3.22

Data are presented as mean±SEM.

Table 3. Changes from the beginning of the experimental period in the three groups
Semen parameter
Period of abstinence (days)
Semen volume (mL)
Sperm concentration (×106/mL)
Sperm motility (%)
Abnormal sperm rate (%)
Semen plasma WBC (×106/mL)
Straight-line velocity (μm/s)
Curvilinear velocity (μm/s)
Straightness (%)
Amplitude of lateral head displacement (Hz)Sperm head pitch (μm)
Degree of sperm-nucleus damage (%)
Data are presented as mean±SEM.
*
p<0.05 vs control group.

Control group
6th week
12th week
1.5±2.5
0.2±3.7
0.45±0.28
0.40±0.41
12.8±20.6-13.0±9.46-3.24±3.35-0.87±4.77
0.89±1.36
4.21±2.13
0.05±0.15-0.02±0.16-0.67±2.51-1.87±1.00
0.54±4.72-1.80±2.9-5.33±2.57-2.16±2.26
0.09±0.12-0.04±0.06-0.96±0.87
2.07±0.86
10.19±2.83
4.15±2.50

Antioxidant group
6th week
12th week
1.2±1.3-1.1±0.7-0.01±0.20-0.48±0.22*
5.38±7.80-11.9±5.48-2.28±3.76
5.24±5.28-2.67±1.74-2.41±1.46
0.02±0.17-0.03±0.09
0.63±2.20-1.02±1.59
2.86±3.45-2.84±3.42-0.91±1.77-1.66±2.41
0.09±0.06-0.06±0.04
0.19±0.45-0.87±0.79
2.30±2.95
1.03±2.58

Tomato juice group
6th week
12th week-0.8±1.5
0.3±1.5-0.13±0.23-0.21±0.20*
15.9±7.29
0.64±6.76
5.87±3.26*
0.08±2.93
0.82±1.77
1.56±1.46-0.01±0.18-0.21±0.08*
0.65±1.36
1.86±1.28
2.67±2.74
3.27±2.66-1.27±1.55
0.42±1.87
0.06±0.05
0.42±0.37-0.94±0.52-0.57±0.55
2.72±2.94
0.42±2.94

Tomato juice and male infertility

Figure 2. Semen plasma malondialdehyde levels in the threegroups. Data are presented as mean±SEM.

group: 6) because of a freezer problem. Decreasing trendwith time was observed in the antioxidant and tomato
juice groups, but was not statistically significant.
Changes in semen parameters of each experimentalgroup are shown in Table 2. There was no statisticallysignificant difference in the parameters for antioxidant or
tomato juice groups compared to the control group.
Changes in sperm parameters from the beginning of theexperimental period are summarized in Table 3. In thetomato juice group, the amount of decrease of seminal
plasma WBCs was statistically significant, compared tothe control group at the 12th week (p=0.039); an increasein sperm motility was also statistically significant, compared to the control group at the 6th week (p=0.019). In
the tomato juice and antioxidant groups, the amount ofdecrease of semen volume was statistically very significant, compared to the control group at the 12th week (tomato juice group vs control group; p=0.037, antioxidantgroup vs control group; p=0.035).
DISCUSSION
Oxidative stress with excessive generation of reactive
oxygen species (ROS) may play an important role in maleinfertility.5 A prospective study demonstrated that men
with higher ROS generation had only about a 15% chanceof pregnancy, compared to men with low ROS.16 Although which reactive oxygen plays a critical role in oxidative damage in the sperm is unknown, Griveau et al
proposed in an in vitro study that singlet oxygen intervened in the lipoperoxidation process in human spermatozoa.19 Lycopene is a major carotenoid in tomatoes andis one of the most efficient singlet oxygen quenchers.11
We therefore hypothesized that regular consumption of
tomato juice rich in lycopene would potentially result in
benefits to male fertility by enhancing antioxidant capacity in sperm. To investigate this hypothesis, we set seminal
plasma lycopene levels and sperm parameters as the main
endpoints of this study in infertile men. We observed asignificant increase in seminal plasma lycopene levels
after consumption of tomato juice for 12 weeks. Many
reports have shown that consumption of tomatoes andtomato products increases lycopene levels in various human biological fluids, such as blood20 and breast milk,21
but there are few reports on an increase in seminal plasma.22 In our study, seminal plasma lycopene level at the12th week was higher than that at the 6th week; the rate of69

lycopene accumulation in seminal plasma is lower than inblood.23
ROS are hypothesized to affect sperm function throughperoxidation of polyunsaturated fatty acids in the sperm
plasma membrane.5,6 MDA is an important marker ofseminal plasma peroxidation. Seminal plasma MDA levels were significantly higher in infertile compared to fertile men.24,25 Moreover, seminal plasma MDA level was
negatively correlated with sperm motility and counts infertile and infertile men. In our study, we could not determine the effects of antioxidants or tomato juice on
seminal plasma MDA levels because of inadequate sample size. Further investigation is needed to elucidate theeffects.
Consumption of tomato juice decreased semen WBCsin the present study. The WHO defines leukocytospermia
as semen WBCs >106/mL. Although the association between semen WBCs and quality is still a matter of debate
in the literature,26 many studies reported that semen
WBCs negatively affect semen quality as a result of ROS
produced by WBCs.27-29 In this study, the effects of a decrease of semen WBCs on semen quality in the tomato
juice group were uncertain, because the baseline value
was in the normal range (0.63±0.08×106/mL).
We recruited subjects with low sperm concentration(<20×106/mL) or low sperm motility (<50%). After regular consumption of tomato juice, there was no statisticalchange in sperm concentration, but there was significant
improvement in sperm motility at the 6th week. Various
authors recognize semen parameters such as sperm motility, concentration, and morphology as vital for assessment of fertility. Semen parameters were also correlatedwith in vitro oocyte fertilization rates.30-32 Our results
indicated that tomato juice consumption for 6 weeks may
have a positive effect on asthenozoospermia by improving sperm motility. However, the improvement was notobserved at the 12th week in the same group. This might
be dependent upon the large variation in sperm motility
within an individual, which is influenced by many factors,
such as a period of sexual abstinence. The usefulness of
tomato juice consumption for sperm motility should be
evaluated in further prospective studies.
Gupta et al15 reported that consumption of 2 mg of lycopene twice a day improved sperm motility in men with
idiopathic nonobstructive oligo/astheno/teratozoospermia.
The amounts of vitamin C (38 mg) and vitamin E (3 mg)
in the can of tomato juice that we used were much smaller
than those in the antioxidant pills (vitamin E 200 mg/day,vitamin C 200 mg/day, glutathione 400 mg/day) in thisstudy. This suggests that lycopene is the active ingredientin tomato juice that improves sperm motility.
In our study, the semen volume was decreased at the12th week in both the antioxidant and tomato juice groups.
There are many reports that antioxidant intake either improves or has no effect on the semen volume, but no reports show decreases in these parameters. Semen volume
is affected by daily habits, such as smoking33 and cholesterol intake.34 In this study, the subjects were not proscribed any daily activities, except for eating lycopenerich foods, including tomatoes, in the feeding period.
Therefore, we could not determine the effects of lifestyle,but these may be a factor, rather than consumption of

70

Y Yamamoto, K Aizawa, M Mieno, M Karamatsu, Y Hirano, K Furui, T Miyashita, K Yamazaki, T Inakuma and I Satotomato juice and intake of antioxidant pills.
Antioxidant compounds (vitamins, glutathione, ubiquinol, and carnitine alone) were administered to maleinfertile patients, because of positive effects on semen
parameters.35,36 In a small trial in 14 infertile men who
received the same three antioxidants as in this study (vitamin E 200 mg/day, vitamin C 200 mg/day, glutathione
400 mg/day), there were significant positive effects onsperm concentration.37 Meanwhile, there are many reportsthat consumption of antioxidants has no effect on semenquality, so the effect of this antioxidant treatment on
sperm quality is still an open question.38,39 Moreover, themechanisms by which antioxidant treatment affect sperm
quality are not yet known. It was reported that many antioxidants, like vitamin E, vitamin C, and glutathione, were
present in seminal plasma.40-42 However, whether theseantioxidants accumulate in the sperm after long-term oral
intake is still unclear.
In the present study, intake of antioxidants (vitamin E,
vitamin C, glutathione) yielded no statistical change insemen parameters, except for sperm volume. To confirm
the effects of antioxidant pills on male infertility, more
research is needed.
Conclusion
In conclusion, regular consumption of tomato juice seems
to improve sperm motility in infertile patients. This is thefirst report to show that commercially available food,such as tomato juice, might benefit male infertility. The
active ingredient in tomato juice that improves sperm
motility may be lycopene, but the mechanism is still unknown. To confirm the effect of tomato juice in detail, we
are now planning a large-scale interventional study.
ACKNOWLEDGEMENTS
Measurement of semen parameters in this work was supportedby Miki Muroi and Mami Enjoji.
AUTHOR DISCLOSURESThe authors declare that they have no competing interests.
REFERENCES
1. World Health Organization. Report of the Meeting on thePrevention of Infertility at the Primary Health Care Level.
Geneva: World Health Organization; 1983.
2. Bablok L, Dziadecki W, Szymusik I, Wolczynski S, Kurzawa R, Pawelczyk L, Jedrzejczak P, Hanke W, Kaminski P,
Wielgos M. Patterns of infertility in Poland – multicenter
study. Neuro Endocrinol Lett. 2011;32:799-804.
3. Safarinejad MR. Infertility among couples in a populationbased study in Iran: prevalence and associated risk factors.
Int J Androl. 2008;31:303-14. doi: 10.1111/j.1365-2605.
4. Mostafa T. Cigarette smoking and male infertility. J Adv
Res. 2010;1:179-86. doi: 10.1016/j.jare.2010.05.002
5. Walczak-Jedrzejowska R, Wolski JK, Slowikowska-Hilczer
J. The role of oxidative stress and antioxidants in male fertility. Cent European J Urol. 2013;66:60-7. doi: 10.5173/ ceju.2013.01.art19.
6. Schuppe HC, Meinhardt A, Allam JP, Bergmann M,
Weidner W, Haidl G. Chronic orchitis: a neglected cause ofmale infertility? Andrologia. 2008;40:84-91. doi: 10.1111/j.
1439-0272.2008.00837.x.
7. Oborna I, Wojewodka G, De Sanctis JB, Fingerova H, Svobodova M, Brezinova J, Hajduch M, Novotny J, Radova L,

Radzioch D. Increased lipid peroxidation and abnormal fatty
acid profiles in seminal and blood plasma of normozoospermic males from infertile couples. Hum Reprod. 2010;25:
308-16. doi: 10.1093/humrep/dep416.
8. Ford WC. Regulation of sperm function by reactive oxygen
species. Hum Reprod. 2004;10:387-99. doi: 10.1093/hum
upd/dmh034.
9. Agarwal A, Saleh RA, Bedaiwy MA. Role of reactive oxygen species in the pathophysiology of human reproduction.
Fertil Steril. 2003;79:829-43. doi: 10.1016/S0015-0282(02)04948-8.
10. Henkel R, Kierspel E, Stalf T, Mehnert C, Menkveld R,
Tinneberg HR, Schill WB, Kruger TF. Effect of reactive
oxygen species produced by spermatozoa and leukocytes onsperm functions in non-leukocytospermic patients. Fertil
Steril. 2005;83:635-42. doi: 10.1016/j.fertnstert.2004.11.022.
11. Di Mascio P, Kaiser S, Sies H. Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch
Biochem Biophys. 1989;274:532-8. doi: 10.1016/0003-9861(89)90467-0.
12. Kong KW, Khoo HE, Prasad KN, Ismail A, Tan CP, Rajab
NF. Revealing the power of the natural red pigment lycopene. Molecules. 2010;15:959-87. doi: 10.3390/molecules1
5020959.
13. Rao AV, Rao LG. Carotenoids and human health. Pharmacol Res. 2007;55:207-16. doi: 10.1016/j.phrs.2007.01.012.
14. Stahl W, Schwarz W, Sundquist AR, Sies H. Cis-trans isomers of lycopene and beta-carotene in human serum and tissues. Arch Biochem Biophys. 1992;294:173-7.
15. Gupta NP, Kumar R. Lycopene therapy in idiopathic maleinfertility - a preliminary report. Int Urol Nephrol. 2002;34:
369-72. doi: 10.1023/A:1024483520560.
16. WHO Laboratory Manual for the Examination of Human
Semen and Sperm-Cervical Mucus Interaction 4th Edition.
World Health Organization. Cambridge: Cambridge University Press; 1999.
17. Aitken RJ, Irvine DS, Wu FC. Prospective analysis of sperm
oocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am J Obstet Gynecol.
1991;164:542-51. doi: 10.1016/j.fertnstert.2006.02.111.
18. Takihara H, Baba Yshizu K, Ueno T, Sakatoku J. Testiculardevelopment following unilateral orchiopexy measured by a
new orchiometer. Urology. 1990;36:370-2. doi: 10.1016/00
90-4295(90)80252-I.
19. Griveau JF, Dumont E, Renard P, Callegari JP, Le Lannou
D. Reactive oxygen species, lipid peroxidation and enzymatic defence systems in human spermatozoa. J Reprod Fertil. 1995;103:17-26. doi: 10.1530/jrf.0.1030017.
20. Rao AV. Processed tomato products as a source of dietarylycopene: bioavailability and antioxidant properties. Can J
Diet Pract Res. 2004;65:161-5. doi: 10.3148/65.4.2004.161.
21. Allen CM, Smith AM, Clinton SK, Schwartz SJ. Tomato
consumption increases lycopene isomer concentrations inbreast milk and plasma of lactating women. J Am Diet Assoc. 2002;102:1257-62. doi: 10.1016/S0002-8223(02)9027
8-6.
22. Goyal A, Chopra M, Lwaleed BA, Birch B, Cooper AJ. The
effects of dietary lycopene supplementation on human seminal plasma. BJU Int. 2007;99:1456-60. doi: 10.1111/j.146
4-410X.2007.06804.x.
23. Stahl W, Sies H. Uptake of lycopene and its geometricalisomers is greater from heat-processed than from unprocessed tomato juice in humans. J Nutr. 1992;122:2161-6.
24. Mehrotra A, Katiyar DK, Agarwal A, Das V, Pant KK. Roleof total antioxidant capacity and lipid peroxidation in fertile
and infertile men. Biomed Res. 2013;24:347-52.
25. Layali I, Tahmasbpour E, Joulaei M, Jorsaraei SG, Far-

Tomato juice and male infertility
zanegi P. Total antioxidant capacity and lipid peroxidationin semen of patient with hyperviscosity. Cell J. 2015;16:554-9.
26. Lackner JE, Agarwal A, Mahfouz R, du Plessis SS, Schatzl
G. The association between leukocytes and sperm quality isconcentration dependent. Reprod Biol Endocrinol. 2010;8:
12. doi: 10.1186/1477- 7827-8-12.
27. Aitken RJ, West K, Buckingham D. Leukocytic infiltration
into the human ejaculate and its association with semenquality, oxidative stress, and sperm function. J Androl. 1994;
15:343-52. doi: 10.1002/j.1939-4640.1994.tb00462.x.
28. Whittington K, Harrison SC, Williams KM, Day JL,
McLaughlin EA, Hull MG, Ford WC. Reactive oxygen species (ROS) production and the outcome of diagnostic testsof sperm function. Int J Androl. 1999;22:236-42. doi: 10.104
6/j.1365-2605.1999.00174.x.
29. Sharma RK, Pasqualotto AE, Nelson DR, Thomas AJ Jr,
Agarwal A. Relationship between seminal white blood cellcounts and oxidative stress in men treated at an infertility
clinic. J Androl. 2001;22:575-83. doi: 10.1002/j.1939-46
40.2001.tb02217.x.
30. Oehninger S, Kruger T. The diagnosis of male infertility bysemen quality. Clinical significance of sperm morphology
assessment. Hum Reprod. 1995;10:1037-8.
31. Enginsu ME, Dumoulin JC, Pieters MH, Evers JL, Geraedts
JP. Predictive value of morphologically normal sperm concentration in the medium for in-vitro fertilization. Int J Androl. 1993;16:113-20. doi: 10.1111/j.1365-2605.1993.tb011
63.x.
32. Mashiach R, Fisch B, Eltes F, Tadir Y, Ovadia J, Bartoov B.
The relationship between sperm ultrastructural features andfertilizing capacity in vitro. Fertil Steril. 1992;57:1052-7.
33. Ramlau-Hansen CH, Thulstrup AM, Aggerholm AS, Jensen
MS, Toft G, Bonde JP. Is smoking a risk factor for decreased semen quality? A cross-sectional analysis. Hum Reprod. 2007;22:188-96. doi: 10.1093/humrep/del364.

71

34. Chavarro JE, Mínguez-Alarcón L, Mendiola J, CutillasTolín A, López-Espín JJ, Torres-Cantero AM. Trans fatty
acid intake is inversely related to total sperm count in young
healthy men. Hum Reprod. 2014;29:429-40. doi: 10.1093/
humrep/det464.
35. Sikka SC, Rajasekaran M, Hellstrom WJG. Role of oxidative stress and antioxidants in male fertility. J Androl. 1995;
16:464-8. doi: 10.1002/j.1939-4640.1995.tb00566.x.
36. Vicari E. Seminal leukocyte concentration and related specific radical oxygen species production in different categories of patients with male accessory gland infection. Hum
Reprod. 2009;14:2025-30. doi: 10.1093/humrep/14.8.2025.
37. Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T.
Increased oxidative deoxyribonucleic acid damage in the
spermatozoa of infertile male patients. Fertil Steril. 1997;68:
519-24. doi: 10.1016/S0015-0282(97)00236-7.
38. Tarin JJ, Brines J, Cano A. Antioxidants may protect against
infertility. Hum Reprod. 1998;13:1415-6. doi: 10.1093/hum
rep/13.6.1415.
39. Comhaire FH, Mahmoud AM, Depuydt CE, Zalata AA,
Christophe AB. Mechanisms and effects of male genitaltract infection on semen quality and fertilizing potential: theandrologist's viewpoint. Hum Reprod Update. 1999;5:393-8.
doi: 10.1093/humupd/5.5.393.
40. Palan P, Naz R. Changes in various antioxidant levels inhuman seminal plasma related to immunoinfertility. Arch
Androl.1996;36:139-43.
41. Colagar AH, Marzony ET. Ascorbic Acid in human seminal
plasma: determination and its relationship to sperm quality.
J Clin Biochem Nutr. 2009;45:144-9. doi: 10.3164/jcbn.08251.
42. Kanďár R, Hájková N. Assay of total glutathione and glutathione disulphide in seminal plasma of male partners ofcouples presenting for a fertility evaluation. Andrologia.
2014;46:1079-88. doi: 10.1111/and.12176.