Document Type : Original Article
Authors
1 Students’ Research Committee, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Reproductive Biotechnology, Reproductive Biomedicine Research Centre, Royan Institute for Biotechnology, ACECR, Isfahan, Iran;Isfahan Fertility and Infertility Center, Isfahan, Iran
3 4Department of Epidemiology and Biostatistics, School of Health, Isfahan University of Medical Sciences, Isfahan, Iran
4 5Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Keywords
Infertility is a disease of the reproductive system defined
by the inability to achieve a clinical pregnancy after 12
months or more of regular unprotected sexual intercourse
(
The relationship between mental status and infertility is
complex as infertility is a risk factor for mental illness and,
psychological distress, can also be a risk factor for infertility (
Dietary antioxidants, mainly vitamins E and C and
β-carotene, have an important role in preventing reactive oxygen species (ROS) production lipid peroxidation (LPO) and DNA damage (
Previous studies showed that deficiencies in antioxidants
levels are major causes of oxidative stress and affect the
mood status; also, they found a relationship between the
level of ROS, mood status, quality of life and fertility, suggesting that various factors can negatively affect spermatogenesis through increasing the levels of ROS, and alteration of the redox balance, which favors oxidants over antioxidants (
This double-blind clinical trial was conducted in winter
and spring of 2018 at Isfahan Fertility and Infertility Center.
Initially, individuals who had a history of primary and secondary infertility, for at least 5 years, were selected. After
a thorough examination, 44 infertile men met the inclusion
criteria. The inclusion criteria included infertile men with
a sperm count less than 20 million per milliliter, normal
sperm <65%, volume <3.0 ml, and average motility <60%,
aged between 25 and 45 years, and not receiving any other
treatments. All patients were required to stop all prior medical treatments for a period of ≥12 weeks and to sign written consent form to enter the study. The exclusion criteria
included having a history of all related disorders including
testicular atrophy, urinary tract infection, testicular torsion,
asthenospermia, azoospermia, genital trauma, inguinal and
genital surgery or other genital diseases such as current genital inflammation and cryptorchidism, anatomical disorders
for example meatal stenosis, or endocrinopathy, use of androgens or antiandrogens, previous hormonal therapy, or use
of cytotoxic drugs, anticoagulants, immunosuppressants or
any antioxidant supplements. Patients with physiological
and psychiatric disorders that may affect sperm and sexual
performance, drug abuse and body mass index (BMI) ≥30
kg/m2, were also excluded (
At the beginning of the study, subjects were randomly assigned to the intervention group [that was supplemented
with 25 mg lycopene (produced by 21st Century Company,
USA) once per day for 12 weeks], or the control group
[that received placebo (starch) for 12 weeks] and patients
were advised to take the palacebo pills at lunch or dinner
meal. We used the standard formula suggested for clinical trials by considering the study with type I error of 5%
(α=0.05) and type II error of 20% (β=0.20) to calculate the
sample size. For randomization group, the intervention 22
patients were assigned to code A, and for the placebo group
22 were assigned to code B, through the method of convenience sampling. Sample size was calculated based on
sperm concentration (
Lifestyle information, medical history, demographic data,
alcohol and tobacco use, and supplement intake were recorded for all participants. Body weight was measured (in
minimal clothing), and body fat was determined by bioelectrical impedance analysis (BIA) method using the Omron
BF-511 set. To measure height, a fixed non-stretchable tape
was used in standing position. Then, BMI was calculated in
kg/m2. The Physical activity level was assessed using the
short form International Physical Activity Questionnaire
(IPAQ) (
Depression, anxiety and stress were assessed using a
21-item Questionnaire (DASS-21) for all participants
pre- and post-intervention. The Cronbach’s alpha coefficient was obtained to show the reliability of the questionnaire (0.84). Similar internal consistency coefficients were reported previously (
A 26-questions form of World Health Organization Quality of Life Questionnaire (WHOQOL) was applied. The
Cronbach's alpha for all sample, non-clinical and clinical
was 0.82, 0.84 and 0.82, respectively (
All data are reported as mean ± standard deviation or frequency (%). The Kolmogorov-Smirnov test was used to evaluate the distribution of data. An independent samples t test was used to analyze the initial variables, dietary intake, mood status and quality of life between the two groups considering normal distribution of variables. A paired t test samples was used to compare the intragroup variables preand post-intervention. To control the confounding variables (energy and carbohydrate), a MANCOVA test was applied to determine the differences between the groups post-intervention. Statistical analysis was performed using SPSS software version 16 (SPSS Inc., Chicago, IL, USA). A P<0.05 was considered significant.
In total, 44 patients were recruited for this clinical trial
and divided into two groups of 22 individuals; finally,
38 subjects completed the study: 19 in the lycopene
group and 19 in the placebo group. In each group 3
participants refused to take supplements or participate
in the final test, and thus, were removed from the study
(
There were no significant differences in depression,
anxiety and stress values between the two groups before
and after adjustment of confounders using MANCOVA
test (
Flowchart of patient recruitment for the double-blind, placebo-controlled, randomized trial of lycopene supplementation in infertile men.
Anthropometric and demographic characteristics and dietary intake of participants at baseline and end
Characteristic | Lycopene n=19 | Placebon=19 | P value | |
---|---|---|---|---|
Age (Y) | 31.89 ± 2.51 | 32.15 ± 2.16 | 0.732 | |
Smoking history | 0.740 | |||
Yes | 7 (36.84) | 8 (42.1) | ||
No | 12 (63.16) | 11 (57.9) | ||
Drinking alcohol history | 0.721 | |||
Yes | 6 (31.57) | 14 (73.69) | ||
No | 13 (68.43) | |||
Education | 0.896 | |||
≤12 | 3 (15.79) | 4 (21.06) | ||
High school diploma | 7 (36.84) | 6 (31.57) | ||
Bachelor degree or higher | 9 (47.37) | 9 (47.37) | ||
Height (cm) | 177.57 ± 4.79 | 178.78 ± 3.45 | 0.378 | |
Weight (kg) | 85.78 ± 6.10 | 84.78 ± 4.93 | 0.582 | |
Body mass index (kg/m2) | 27.20 ± 1.68 | 26.53 ± 1.53 | 0.206 | |
Body fat (kg) | 28.65 ± 3.37 | 27.98 ± 3.69 | 0.564 | |
Physical activity (MET-h/week) | 30.83 ± 1.95 | 31.0 ± 1.71 | 0.707 | |
Energy intake (kilocalories/day) | ||||
Before | 2251.39 ± 230.54 | 2115.53 ± 175.082 | 0.048 | |
After | 2326.70 ± 200.01 | 2113.63 ± 199.87 | 0.002 | |
Carbohydrate intake (g/d) | ||||
Before | 316.56 ± 34.57 | 294.43 ± 28.0730 | 0.037 | |
After | 330.41 ± 24.83 | 301.02 ± 27.96 | 0.002 | |
Protein intake (g/d) | ||||
Before | 88.04 ± 12.29 | 88.38 ± 8.52 | 0.922 | |
After | 90.15 ± 12.65 | 86.11 ± 9.64 | 0.27 | |
Fat intake (g/d) | ||||
Before | 78.07 ± 16.35 | 72.61 ± 10.487 | 0.229 | |
After | 79.59 ± 16.41 | 71.02 ± 11.11 | 0.068 | |
Lycopene intake (µg/d) | ||||
Before | 4306.46 ± 133 | 4664.39 ± 935.43 | 0.3450.885 | |
After | 4895.57 ± 1362.35 | 4839.47 ± 961.29 | ||
Data are presented as n (%) or mean ± SD. Analysis done using independent-sample t test.
Depression, anxiety and stress score of participants at baseline and end
Variable | Lycopene n=19 | Placebo n=19 | P valuea | P valueb | |
---|---|---|---|---|---|
Depression | |||||
Baseline | 14.10 ± 2.94 | 13.78 ± 3.11 | 0.750 | 0.424 | |
End | 12.73 ± 2.02 | 12.31 ± 2.13 | 0.537 | ||
P valuec | 0.028 | 0.031 | |||
Anxiety | |||||
Baseline | 11.26 ± 2.23 | 11.47 ± 3.04 | 0.809 | 0.510 | |
End | 10.31 ± 2.13 | 10.84 ± 2.43 | 0.483 | ||
P valuec | 0.132 | 0.380 | |||
Stress | |||||
Baseline | 15.05 ± 2.34 | 14.52 ± 2.73 | 0.528 | 0.700 | |
End | 14.52 ± 2.09 | 14.21 ± 1.98 | 0.636 | ||
P valuec | 0.331 | 0.546 | |||
Data are reported as mean ± SD. a; Analysis done using Independent-sample t test, b; Multivariate analysis of covariance done following adjustment (for energy and carbohydrate), and c; Analysis done using paired-sample t test.
The effect of lycopene supplementation on four domains of quality of life (physical, psychological, social, and environmental) is presented in Table 3. There were no significant differences in all domains between the two groups before and after adjustment of confounders using MANCOVA test. Aside from the psychological domain in the lycopene group (P=0.049), no significant changes were observed in other quality of life domains as assessed by pair t test.
Quality of life score of participants at baseline and end
Variable | Lycopene n=19 | Placebo n=19 | P valuea | P valueb | |
---|---|---|---|---|---|
Physical health (%) | |||||
Baseline | 67.73 ± 11.21 | 70.31 ± 17.017 | 0.585 | 0.743 | |
End | 71.89 ± 10.20 | 2.89 ± 15.34 | 0.814 | ||
P valuec | 0.111 | 0.238 | |||
Psychological health (%) | |||||
Baseline | 66.36 ± 13.75 | 69.00 ± 19.39 | 0.632 | 0.998 | |
End | 69.52 ± 10.99 | 71.57 ± 15.47 | 0.640 | ||
P valuec | 0.049 | 0.233 | |||
Social relation health (%) | |||||
Baseline | 72.05 ± 17.57 | 71.31 ± 22.28 | 0.911 | 0.680 | |
End | 71.89 ± 12.16 | 72.89 ± 17.50 | 0.839 | ||
P valuec | 0.936 | 0.480 | |||
Environmental health (%) | |||||
Baseline | 67.36 ± 13.38 | 65.57 ± 21.45 | 0.760 | 0.578 | |
End | 67.42 ± 11.25 | 65.52 ± 15.95 | 0.675 | ||
P value c | 0.977 | 0.980 | |||
Data are reported as mean ± SD. a; Analysis done using Independent-sample t test, b; Multivariate analysis of covariance done following adjustment (for energy and carbohydrate), and c; Analysis done using paired-sample t test.
This study was a randomized clinical trial designed to evaluate the effect of lycopene supplementations on depression, anxiety, stress, and quality of life. To the best of our knowledge this is the first study that assessed the effect of lycopene on mood state and quality of life scale. No significant differences were observed between the groups in terms of depression, anxiety and stress scores, or quality of life, after lycopene supplementation. Energy and carbohydrate intakes were different.
Our findings were in line with those reported by Tsuboi
et al. (
The antidepressant properties of lycopene were also
observed in animal studies; for instance, Zhang et al.
administered 6 mg/kg body weight per day lycopene for
seven days to mice, and observed attenuated depressionlike behaviors (
Depression, anxiety, and stress are among the most
prevalent mood disorders in the world (
Besides, new studies point out that psychiatric disorders
are resulted from alterations, not only in brain function,
but also in neuronal plasticity (
Another putative explanation for the potential protective
effect of lycopene is based on its protective role against
atherosclerotic cardiovascular diseases and cancer (
The non-significant nature of our findings might be due to the relatively short duration and/or low dosage of administered lycopene, which might have been not high enough to exert stronger acute effects, highlighting the need for further work to investigate the impact of both duration and dosage. Nevertheless, contrary to contemporary theories, lycopene did not show any clinical effects on psychiatric disorders. It is noteworthy that within-group analysis showed that depression scores decreased in both groups compared to the baseline values. This could simply be due to the fact that the patients merely felt they are getting better while no clinical response to lycopene was evident. However, due to some constraints, we were unable to measure the seminal levels of lycopene, the receptors, and enzymes such as super oxidase dismutase (SOD) and catalase (CAT).
The authors of the present study strongly suggest that further work using varying doses, done in larger sample sizes, including both genders, and for longer periods should be conducted to evaluate the effects of potent antioxidants on different psychological aspects of infertile individuals.
12-week lycopene supplementation, did not have any significant effects on psychiatric disorders and quality of life, urgently highlighting the need for further evidence of the efficacy of lycopene, for improving mood status and quality of life in infertile men.