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Journal of Herbmed Pharmacology
J Herbmed Pharmacol. 2018; 7(4): 306-312.
Effect of garlic (Allium sativum) on male fertility: a systematic
review
Hadis Musavi1
ID
, Malihe Tabnak2, Farzaneh Alaei Sheini3, Maryam Hasanzadeh Bezvan4, Fardin Amidi5, Mojtaba
Abbasi6*
ID
1Department of Biochemistry, Faculty of Basic Science, Razi University Kermanshah, Kermanshah, Iran
2Department of Basic Sciences, East Tehran Branch, Islamic Azad University, Tehran, Iran
3Department of Biology, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
4Department of Microbiology, Shahr-e-Qods Branch, Islamic Azad University, Tehran, Iran
5Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
6Veterinary Medicine, Faculty of Veterinary Medicine, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
*Corresponding author: Mojtaba Abbasi, Tel: +989131852230, Email:
Dr_Abbasi_m@yahoo.com
Implication for health policy/practice/research/medical education:
This article presented useful information about garlic, especially on fertility and reproduction system which could help
pharmacists and scientists in the provision of new drugs.
Please cite this paper as: Musavi H, Tabnak M, Alaei Sheini M, Hasanzadeh Bezvan M, Amidi F, Abbasi M. Effect of garlic
(Allium sativum) on male fertility: a systematic review. J Herbmed Pharmacol. 2018;7(4):306-312. doi: 10.15171/jhp.2018.46.
Introduction: Fertility in men mainly depends on the number, quality, motility, and
morphology of the sperms, and disruption of each of these factors leads to infertility. A large
number of couples suffer from infertility problems. Among the various therapies, medicinal
herbs are used in many countries to treat male infertility. Current systematic review was
conducted to study the effects of garlic on male fertility.
Methods: The information of this systemat ic review was collected by searching the key words:
treatment, fer tility, infertilit y, male, herbal medicine, ga rlic, Allium sativu m, medicinal plant,
sperm, sex hormones, testis and spermatogenesis in international databases such as: Web of
Science (ISI), PubMed, Scopus and Embase until March 2018. This study was conducted in
accordance with the PRISMA statement for systematic reviews and meta- analysis. and the
SYRCLE risk of bias tool was used for qualitative assessment.
Results: A total of 18 experimental studies were included in the study. Thirteen studies
evaluate d garlic and 5 studie s compared garlic effec t with adria mycin, titanium d ioxide, fura n,
vitamin E, N-acetylcysteine and cadmium. All studies were conducted in in vivo condition.
The results of the studies indicated the potential effect of garlic on enhancing fertility and
spermatogenesis, increasing the level of testosterone and improving the testicular structure.
Conclusion: Garlic can increase fertility probably due to its antioxidant properties. However,
more clinical trials are recommended.
A R T I C L E I N F O
Keywords:
Garlic
Allium sativum
Fertility
Infertility
Spermatogenesis
Medicinal plants
Article History:
Received: 7 March 2018
Accepted: 10 September 2018
Article Type:
Review
A B S T R A C T
Introduction
Failure to have a child is an unpleasant event in the lives of
infertile people (1). Inability to become pregnant after one
year of regular intercourse, without using contraception,
is defined as infertility (2). About 30%-50% of the causes
of infertility are related to male problems (3). Each
day, the number of medical reports about the extent of
infertility in the world increases, according to a systematic
review in this regard, about 48.5 million couples around
the world affected by this problem (4). The total mean
of infertility in Iran is estimated about 11%-19%, which
is more in the age group of 20-39 years (5). Infertility is
a multi-parameter phenomenon with a wide range of
factors that affects spermatogenesis and sperm quality
(6). Spermatogenesis is a process in which male sex cells
are produced and the disorder in each of these stages
can cause infertility (7). Fertility in men depends largely
on the number, quality, motility, and morphology of the
sperm, and the disruption of each of these factors leads
to infertility in men (3). Infertility, as a psychological
crisis, imposes a lot of stress on infertile couples and in
different ways threatens their mental health. The most
http://www.herbmedpharmacol.com doi: 10.15171/jhp.2018.46
Journal of Herbmed Pharmacology, Volume 7, Number 4, October 2018
http://www.herbmedpharmacol.com 307
Eect of garlic on male fertility: a systematic review
emotional and psychological problems of infertile couples
are disappointment, frustration, fear and anxiety, and are
less associated with anger and aggression. However, the
rate of divorce and remarriage among infertile couples
has risen. In addition to mental problems, the economical
treatment of infertility imposes a relative high cost on
infertile couples (8).
Nowadays, various methods are used to treat infertility,
including: hormone therapy, surgical procedures, assisted
reproductive technology (ART) that include in vitro
fertilization (IVF), intra uterine insemination (IUI), zygote
intrafallopian transfer (ZIFT), gamete intrafallopian
transfer (GIFT), intracytoplasmic sperm injection (ICSI)
and third-party fertilization (donation eggs, donation
sperm, uterus, and donated embryos) (9).
ART is one of the costly treatments among infertile
couples, but many people are not able to do so because
financial problems, and surgical procedures have a
lot of stress and complications for the family, and in
addition they are expensive (8). Hormone therapy is
also prohibited in some people, and in many people
with impaired hypothalamic-pituitary-gonadal axis
function, this treatment is not responsive therefore, due
to individual and social problems caused by infertility,
couples always try to find low-cost, safe and effective
treatments (10). Regarding the problems that have been
observed among couples and the high costs of medical
interventions, people have turned to complementary
medicine (11). Among different therapeutic methods,
herbs are used in many countries to treat male infertility
(1,12,13). Plants are more affordable and accessible than
invasive and chemical treatments (14). Medicinal herbs
with high antioxidant properties are used to treat sperm
abnormalities, sexual dysfunction, erectile and ejaculatory
disorders (1,15). Among the plants that improve male
fertility, celery (16), fennel (17), black seed (18), German
chamomile (19), saffron (20), Fumaria parviflora (21),
Origanum vulgare (22) and carrot (23) can be mentioned.
Some plants change the number and motility of the sperm
by changing sex hormones. Other plants with androgenic
properties affect the hypothalamus-pituitary axis and
increase sex hormones (24). Garlic with its antioxidant
properties, have been shown to increase the weight of the
epididymis, seminal vesicles and increases the number of
sperms (25). Garlic is one of the most potent and most
prominent species of plants, which is a part of the onion
family (7). Garlic has been known since 5000 years ago. In
ancient times, Babylonians, Egyptians, Vikings, Chinese,
Greeks, Romans and Hindus used garlic (26). In 3000 BC
garlic was used for heart disease, arthritis, uterine disease,
pulmonary disease, skin diseases, diarrhea, headache,
wound healing and tumor (27,28). It is native to Western
Asia, also found in most regions of Iran, especially in the
northern regions (29). The perennial plant, has a height of
100-300 cm, has flowers in pink or green (16). It is used
commonly as a medicinal herb and food flavor, and it is one
of the herbs that have a long history of medical uses (30).
Garlic contains many compounds, including vitamins B2,
B6, B1, A and C, a lot of antioxidants, flavonoids, sulfur
compounds and allicin (7). Allicin (dialkly thiosulfinate)
plays a key role in the garlic medicinal properties,
however, this compound is not found in fresh garlic, and
made by action of allinase on alliin (S-alkyl-l-cysteine
sulfoxide). Ajoene is another important compound in
garlic (Figure 1) (31). Garlic protects the liver and has
anticholesterolemic, antithrombotic, antihypertensive and
antimicrobial activity (30), and consumption of garlic acts
like insulin receptor and reduces glucose levels in diabetic
patients (3). Solving infertility problem is a fundamental
issue in every community’s health system. Considering
the complications and limitations of chemical drugs and
surgical procedures, and according to the mentioned
therapeutic effects of garlic, this systematic review was
conducted to investigate the effects of garlic on male
fertility.
Methods
Study protocol
Current systematic review was reported in accordance
with PRISMA (Preferred Reporting Items for Systematic
Reviews and Meta-analyses) guidelines (32). In this study,
the search process was done aimed to find studies in
English without time limitations.
Search strategy
Data were collected by searching the key words: treatment,
fertility, infertility, male, herbal medicine, garlic, medicinal
plant, sperm, sex hormones and spermatogenesis in
international databases such as: Web of Science (ISI),
PubMed, Scopus and Embase until March 2018.
Inclusion criteria
- To conduct experimental studies or clinical trials
- Randomization in studies
- Evaluation of fertility, spermatogenesis or male sex
hormones
- Mentioning of ethical considerations in articles
Figure 1: The main compounds of garlic.
Journal of Herbmed Pharmacology, Volume 7, Number 4, October 2018 http://www.herbmedpharmacol.com
308
Musavi et al
Exclusion criteria
- Absence of proper sampling method in studies
- Evaluation of fertility in female, not male, samples
- Not mentioning moral considerations
Selection of studies and data extraction
The articles’ information was reviewed independently by
two authors based on inclusion and exclusion criteria.
Finally, both of authors classified the information and, in
cases that the information was inconsistent, the comments
of the third author were used. The information obtained
from the articles was entered into the checklist considering
the quality approval of the articles. The checklist
contained: author’s name, year of the study, type of study,
molecular change, type of sample, type of administration,
dosage, part of plant and period of extract administration.
SYRCLE risk of bias tool was used for assessment of the
quality. This tool is an advanced and improved model of
the past quality assessment tools that is specific to animal
and pre-clinical studies (33) and solve some of defects of
the previous tools that was related to clinical trials.
Results
In the first stage of search, 980 articles were found.
After removing duplicates and unrelated articles, 18
experimental studies included in this systematic review
(Figure 2).
Thirteen studies evaluated garlic and 5 studies compared
garlic effects with other drugs. A study compared aged
garlic extract with adriamycin, a study compared aged
garlic extract with titanium dioxide, a study compared
garlic oil extract with furan, a study compared garlic blue
extract with vitamin E and N-acetyl cysteine and a study
compared garlic extract and onion with cadmium.
Qualitative assessment showed that most studies were in
high risk for bias. In most of these studies, randomization
in animal housing, randomization in sampling, researcher
and statistical analyzers blinding were not me n tioned
clearly (Tab l e 1).
In 10 studies garlic extract was prescribed as crude
plant and powder for animals. The maximum sample
size was 62 mice and the lowest sample size was 10 mice
that were examined in experimental studies. All studies
were conducted in the in vivo condition. The control
group received distilled water, normal saline or powder
containing starch, and the treatment group received
aged garlic extract, adriamcyin, titanium dioxide, garlic
oil, N-acetylcyseinne, vitamin E, cadmium, cooked
garlic or garlic juice. The treatment period varied
from 7 to 120 days and complications such as impaired
spermatogenesis, apoptosis, abnormal sperm, decreased
sperm motility, seminal vesicle disorder, increased blood
cholesterol, leukocytosis, decreased testicular weight,
decreased Leydig cells, increased prostate weight and
increased cortisol were mentioned in the studies. All of
these complications were reported as chemical substances
toxicity. Further information is presented in Tab l e 2.
Discussion
The present study was a systematic review of the effects of
garlic on fertility. In general, in this paper, 18 studies were
reviewed. Thirteen studies were conducted on the effect of
garlic on fertility treatment. Due to the lack of side effects,
as well as containing flavonoids, vitamins, fructose and
sulfur compounds, garlic can help with neutralizing free
radicals (1). Sulfur compounds in garlic, with a direct effect
on the metabolism of cytochrome P450 and glutathione
-s-transferase, have a protective effect on spermatogenesis.
In addition to sulfur compounds, garlic has antioxidant
properties and can increase fertility by reducing lipid
peroxidation (32). Given the above mentioned factors,
garlic is recommended for the treatment of infertility. In
a study by Asadpour et al it was indicated that garlic has
antioxidant activity due to presence of vitamin E, which
prevents oxygen peroxide (49). Also, the results of the
study by Nasr showed that garlic antioxidant properties
can reduce the toxicity of harmful drugs on the testes and
increase the spermatogenesis and fertility in men (35).
In the study by Akabawy and Sherif, it was concluded
that garlic inhibited caspase-3 and cytochrome P450
2E1 (CYP2E1) enzymes, which had a toxic effect on the
testes and, by decreasing these two enzymes, improved
the testicular performance and spermatogenesis (37).
6
Figure 2: Trend of screening and choosing articles based on PRISMA guidelines
Thirteen studies evaluated garlic and 5 studies compared garlic effects with other drugs. A study compared
aged garlic extract with adriamycin, a study compared aged garlic extract with titanium dioxide, a study
compared garlic oil extract with furan, a study compared garlic blue extract with vitamin E and N-acetyl
cysteine and a study compared garlic extract and onion with cadmium.
Records identified through
database searching
(n = 968)
Screening
Included
Eligibility
Identification
Additional records identified
through other sources
(n = 12)
Records after duplicates removed
(n = 85)
Records screened
(n = 85)
Records excluded
(n = 65)
Full-text articles assessed
for eligibility
(n = 20)
Full-text articles excluded,
with reasons
(n =2)
Studies included in
qualitative synthesis
(n = 18)
6
Figure 2: Trend of screening and choosing articles based on PRISMA guidelines
Thirteen studies evaluated garlic and 5 studies compared garlic effects with other drugs. A study compared
aged garlic extract with adriamycin, a study compared aged garlic extract with titanium dioxide, a study
compared garlic oil extract with furan, a study compared garlic blue extract with vitamin E and N-acetyl
cysteine and a study compared garlic extract and onion with cadmium.
Records identified through
database searching
(n = 968)
Screening
Included
Eligibility
Identification
Additional records identified
through other sources
(n = 12)
Records after duplicates removed
(n = 85)
Records screened
(n = 85)
Records excluded
(n = 65)
Full-text articles assessed
for eligibility
(n = 20)
Full-text articles excluded,
with reasons
(n =2)
Studies included in
qualitative synthesis
(n = 18)
Figure 2. Trend of screening and choosing articles based on
PRISMA guidelines.
Journal of Herbmed Pharmacology, Volume 7, Number 4, October 2018 http://www.herbmedpharmacol.com
309
Musavi et al
Hammami and Abdelmalik (38) concluded that garlic
contains phytoestrogens, which have a direct effect on
estrogen. It is a precursor to testosterone production, so
it is possible that garlic stimulates the sexual cells and
sex hormones (38,43). The results in the study by Oi et al
indicated that garlic supplementation boosts LH from the
pituitary gland, and this stimulates testosterone secretion
from the testicles (46). Nonetheless, in the study by
Bahrami et al (7), it was recommended that the cooked
garlic has better therapeutic effects and, while affecting the
reproduction of the sexual cells in testes and epididymis,
improves spermatogenesis (7).
Due to presence of dialyldisulfide in its biochemical
structure, garlic affects the hypothalamic-pituitary
axis. Diallyldisulfide stimulates the basophilic cells and
secretion of LH sex hormones by affecting the anterior
pituitary. LH stimulates Leydig cells in the testes, which
in turn is a precursor to secretion and regulation of
testosterone (50). Also, diallyldisulfide reduces oxygen
free radicals, enhances and strengthens the blood-testis
barrier and increases the circulation in the testicles, thus
protects the sexual organs (39). By increasing blood flow
to the testicles (due to the consumption of garlic), phenol
and phenolic glycosides are released which increase the
glutathione peroxidase enzyme. The role of this enzyme
is to protect sperms in testicular and epididymal tissue
(51). The enzyme protects the sperm from the damage of
free radicals by placement in the plasma membrane and
the nucleus of sperm, epididymal fluid and epididymis,
and leads to ultimate maturation and development of the
sperm (52). Also, garlic can repair and protect the DNA
of the sperm, in addition to sperm maturation through
vitamins C, B, E, which are its potent antioxidants (53).
Approximately 45%-50% of infertility has a male cause,
but nevertheless, 30-45% is due to idiopathic causes (54).
Typically, infertility in men is indicated by oligozoospermia,
asthenozoospermia, or teratozoospermia and varicocele
(55). Recent studies have shown that, in physiological
conditions, reactive oxygen species play a very important
role in intracellular messaging processes. On the other
hand, during the last decade, reactive oxygen species have
been implicated in the development of male infertility,
due to excessive production of reactive oxygen species
or reduced ability of the antioxidant system of the genital
system and sperm. In pathological conditions, reactive
oxygen species result in male infertility through disruption
of the spermatogenesis process, sperm function and
structure, mobility, survival, acrosome reaction, sperm-
to-oocyte coupling and even reduced fertilization and
implantation (56).
Conclusion
Probably, due to the antioxidant power and the absence of
side effects of garlic, it can be useful in enhancing fertility.
Due to the limited number of clinical studies, there is no
definite overall and reassuring result. In order to ensure
the effects of this plant and its compounds, clinical studies
with a larger statistical population, as well as an increase
Table 1. Risk of bias for animal studies, using the SYRCLE risk of bias tool
Study
1 2 3 4 5 6 7 8 9 10
Selecon
bias 1
Selecon
bias 2
Selecon
bias 3
Performance
bias 1
Performance
bias 2
Detecon
bias 1
Detecon
bias 2
Arion
bias
Reporng
bias
Other
potenal
bias
Hajiuon (34) x ✓ ✓ ؟X؟X؟✓ ✓
Nasr (35)✓ ✓ ✓ ؟X X ؟✓ ✓ ✓
Abu Zeid et al (36) ✓ ✓ ✓ ؟ ؟ ؟ ؟ ✓ ✓ ✓
El-Akabawy and El-
Sherif (37)✓ ✓ ✓ ؟ ؟ x؟✓ ✓ ✓
Abdelmalik (38)✓ ✓ x؟X؟X؟✓ ✓
Ouarda and
Abdennour (39)؟✓؟ ؟ ؟ ؟ ؟ ؟ ✓؟
Ghalehkandi (40)✓ ✓ ؟ ؟ X؟ ؟ ؟ ✓ ✓
Bahrami et al (7)✓ ✓ ✓ ؟ ؟ ؟ ؟ x✓؟
Safaei et al (41)✓؟✓؟ ؟ ✓؟ ؟ ؟ ؟
Ola-Mudathir et al
(42)✓ ✓ ✓ ✓ ؟ ؟ ؟ ؟ ✓ ✓
Omotoso et al (25)✓ ✓ ✓ ؟ ؟ ؟ ؟ ؟ ✓ ✓
Nahdi et al (43)✓ ✓ ؟ ؟ ؟ ؟ ؟ ✓ ✓ ✓
Hammami et al (44)✓ ✓ ؟ ؟ ؟ ✓؟ ؟ ✓؟
Hammami et al (45)✓ ✓ ✓ ؟ ؟ ؟ ؟ ؟ ✓ ✓
Oi et al (46)✓ ✓ ؟ ؟ ✓؟ ؟ ؟ ✓ ✓
Lee et al (47)✓ ✓ x؟ ؟ ؟ ؟ ✓ ✓ ✓
Abdullah et al (48)✓ ✓ ✓ ؟ ؟ ✓؟ ؟ ✓ ✓
Asadpour et al (49)✓ ✓ x؟ ؟ ؟ ؟ ✓ ✓ ✓
Eect of garlic on male fertility: a systematic review
Journal of Herbmed Pharmacology, Volume 7, Number 4, October 2018
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Table 2. Effect of garlic on reproductive system and fertility
Eect of garlic Type of extract Duraon of
treatment Dose Administraon Sample
study
Part
used Result Ref.
Eects on sexual
hormones
Hydro alcoholic
extract
30 days 200 and 400 mg/kg Orally Rats Leaves ↓Testosterone levels, ↓Estrogen, ↑Progesterone (34)
Aged garlic extract 7-14 days 250 mg/kg
Orally Rats Seeds ↑Testosterone leves, ↓MDA concentraon, ↑GSH level, ↑GSH-Px, ↑CAT, and
SOD acvity
(35)
Aged garlic extract 65 days 2 mL/kg Orally Rats Leaves ↑Androgen levels (36)
Garlic oil NM 4 mg/kg Orally Rats NM ↓Testosterone levels, ↓Caspase-3, ↓Cytochrome P450 2E1 (37)
NM 120 days 30 g Orally Rats NM ↓Testosterone levels (38)
Eects on
spermatogenesis
and tescular
structure and
other results
NM 14 days 50 g Orally Rabbits Seeds ↑Sperm molity and viability, ↑Sperm speed, ↑White blood counts (39)
Garlic juice 30 days 60 and 120 mg/kg Gavage Rats Seeds ↓Semen MDA acvity, ↓TAS acvity (40)
NM 30 days 5% and 15% of raw garlic and
cooked garlic
Orally Rats Seeds In cooked garlic, ↓Weight Loss, ↑Number of spermatocyte cells, ↑Number
of spermatozoa, ↑Number of sperm cells, ↑Number of Sertoli cells, ↑Tescle
weight, ↑External diameter of the epididymide, ↑The inner diameter of
epididymide, ↑Sperm volume
(7)
Alcoholic extract 30 days 0.05%, 0.1% and 0.2% Orally Rooster Leaves Garlic alcoholic extract 0.2%: ↑Semen volume, ↑Tescle weight, ↑Sperm
counts, ↑Percentage of mobility and sperm biocompability, ↑Laydic cell count
(41)
NM Between 7-21
days
0.5 mL/100 g. BW Gavage Rats Leaves ↑LOP, ↑Glutathione S-transferase, ↑GSH, ↑SOD, ↑CAT, ↑Epididymal sperm
concentraon, ↑Sperm progress molity, ↓Lipid peroxidaon
(42)
Aqueous Extract 28 days 500 and 100 mg/kg Feeding tube Rats Leaves ↓Spermatozoa count, ↓SOD acvity in the blood (25)
NM NM 5%, 10% and 15% Orally Rats Leaves ↑Number of tubules deprived of spermatozoa, ↓Apoptosis of tescular germ
cells, ↓Testosterone levels
(43)
NM 30 days 5%, 10% and 15% of 30 g Orally Rats Seeds ↑CASP3 levels, ↑Caspase inhibitors BIRC3 and BIRC2, ↑IAP inhibitor DIABLO,
↓AMH, RHOX5 and CDKN1B, ↑GATA4
(44)
NM 30 days 5%, 10%, 15% and 30% of 9 g Orally Rats Seeds ↓Prostate weight, ↓Seminal vesicle weight, ↓Testosterone levels, ↑LH levels,
↑Phosphatase acid acvity
(45)
NM 28 days 8 g Intraperitoneal
injecon
Rats - ↑LH levels, ↑Tescular testosterone, ↓Plasma corcosterone (46)
Ethanolic extract 37 days 5, 10, 20 and 40 mg/kg/bw Perorally Rats Leaves ↓Weight loss, ↓Tescular weight, ↑Spermatogenesis (47)
NM 90 days 100 mg/kg/d Intraperitoneal
injecon
Mice Leaves ↑Weight of seminal vesicles and epididymides, ↑Sperm count, ↑Weight loss,
↑WBC, ↓RBC
(48)
NM 35 days 400 mg/kg Gavage Rats Leaves ↑Sperm molity and viability, ↑MDA level, ↑ SOD acvies (49)
NM: not menoned, MDA: malondialdehyde, GSH: glutathione, GSH-px: glutathione peroxidase, SOD: superoxide dismutase, CAT: catalase, TAS: total anoxidant status, BIRC3: baculoviral IAP repeat-containing protein 3, BIRC2: baculoviral
IAP repeat-containing protein2, AMH: an-Mullerian hormone, CDKN1B: cyclin-dependent kinase inhibitor 1B, LH: luteinizing hormone
Journal of Herbmed Pharmacology, Volume 7, Number 4, October 2018
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Eect of garlic on male fertility: a systematic review
in the duration of its administration, comparison with
safe drugs and the determination of the exact molecular
mechanism are recommended.
Authors’ contributions
All authors contributed equally in planning and carrying
out this work. All authors read the manuscript and
confirmed the publication for final version.
Conflict of interests
None.
Ethical considerations
Not applicable.
Funding/Support
There is no financial support for this work.
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